Selenium Intake Modulates Hepato and Nephrotoxic Responses in Rats Exposed to Ferric Nitrilotriacetate (Fe-NTA)

Selenium Intake Modulates Hepato and Nephrotoxic Responses in Rats Exposed to Ferric Nitrilotriacetate (Fe-NTA) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Selenium Intake Modulates Hepato and Nephrotoxic Responses in Rats Exposed to Ferric Nitrilotriacetate (Fe-NTA) Godfrey Rume Kweki, Innocent Ogheneovo Orhonigbe, Benedict Bolakponumigha Iwetan, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7909439/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Ferric nitrilotriacetate (Fe-NTA) is a nephrotoxic compound known to induce acute renal injury through oxidative stress mediated by the Fenton reaction. This study investigated the ameliorating potential of selenium supplementation against Fe-NTA-induced toxicity. Fifty male Wistar albino rats were divided into five groups and acclimatized for two weeks. Except group I and II that served as normal control and negative control, all animals received intraperitoneal injection ( i.p ) of Fe-NTA (3.0 mg/kg) every other day for 14 days. From day 15 to 28, groups III, IV, and V were fed diets supplemented with sodium selenite at doses of 0.06, 0.08, and 0.1 mg, while group II rats were exposed to 3 mg/kg ( i.p ) of Fe-NTA respectively. On day 29, biochemical and histological analyses of blood and tissue samples was conducted. Fe-NTA administration resulted in significant oxidative stress, indicated by elevated malondialdehyde (MDA) levels and decreased antioxidant markers (GSH, SOD, CAT, GST), alongside increased pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and notable hepatic and renal damage. However, Selenium supplementation significantly reversed these effects, improving antioxidant enzymes activities and reducing inflammation along histopathological alterations. These findings from the study show the dietary impact of selenium intake to protect hepatic and renal tissues against Fe-NTA-mediated oxidative and inflammatory toxicity in Wistar rats Ferric Nitrilotriacetate Selenium Selenoproteins glutathione Superoxide dismutase pro-inflammatory cytokines nephrotoxicity hepatoxicity Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 1.0. INTRODUCTION Among the diverse toxicological models used to explore chemical-induced organ toxicity, Ferric Nitrilotriacetate (Fe-NTA) has emerged as a potent inducer of oxidative stress, particularly in the kidneys and liver with severe comorbid effects in brain, testicle, and prostate. (Olivera, 2020 ; Okazaki, 2022 ). Fe-NTA is a nephrotoxic agent, known for inducing acute renal injury via the Fenton chemistry mediation, which generates highly reactive hydroxyl radicals that damage lipids, proteins, and nucleic acids, ultimately leading to cellular dysfunction, inflammation, and apoptosis (Valko et al., 2005 , Tilak and Devasagayam, 2006 ; Toyokuni et al, 2020 ). Primarily, Fe-NTA, is associated with nephrotoxicity. Several studies have also demonstrated its capacity to induce widespread systemic damage, including hepatic and hematological alterations, due to its profound effects on oxidative pathways and cellular integrity (Radwan, 2012 ; Okazaki, 2022 ; Donia et al, 2023 ). The liver, as the primary detoxification organ is specifically susceptible to oxidative damage, which manifests as hepatocellular necrosis, fibrosis, and inflammation (Kweki et al., 2018 , Ichipi-Ifukor et al, 2022 ). Similarly, Fe-NTA exposure results in hematological abnormalities such as reduced red and white blood cell counts, hemolysis, and immune suppression, further complicating its toxicological profile (Olivera, 2020 ; Watkins et al, 2021 ; El-Demerdash et al, 2024 ). As a trace and essential element (Rahbardar et al, 2021 ), selenium plays an essential role in maintaining cellular homeostasis through its incorporation into selenoproteins that function as antioxidants, enzymes in thyroid hormone metabolism, and modulators of immune responses (Achuba and Obaremi, 2018 ). Antioxidative properties of this element is largely attributed to its ability to interacts with antioxidant enzymes of glutathione cycle (Olayanju et al, 2024 ). Selenoprotein P, that are involved in neutralizing reactive oxygen species (ROS) and reducing oxidative stress (Büttner et al, 2020 . Saito, 2022 ; Chaudière, 2023 ). Emerging evidence in recent decades, shows that selenium has garnered significant attention for its potential in mitigating oxidative stress-induced damage in different organs, especially under conditions of chemical exposure or environmental toxicity (Renu et al, 2025 ). However, the deficiency of selenium can be implicative in a range of diseases, including cancer, cardiovascular disease, and immune dysfunction (Shimada et al, 2025 , Barchielli, 2022), when consumed in excess. Symptoms such as selenosis, gastrointestinal distress, and neurological impairments are well documented in link with selenium (Barchielli et al, 2022 ; Adewale et al, 2022 ). This dose-dependent relationship between selenium’s beneficial and toxic effects underscores the importance of understanding its role under different exposure conditions. Further evidences have also highlighted the potential of selenium supplementation to modulate oxidative stress and reduce toxicity associated with various environmental and chemical insults(Achuba and Obaremi, 2018 ), including heavy metal exposure (Ichipi-ifukor et al, 2019 ). Selenium’s ability to enhance antioxidant defense systems has been postulated to counteract the oxidative damage caused by ROS and mitigate the downstream effects of lipid peroxidation, protein oxidation, and DNA damage. However, reports have demonstrated that selenium can alleviate kidney and liver damage induced by toxins such as cadmium, lead, and mercury by restoring antioxidant enzyme activity and reducing pro-inflammatory cytokine levels (Zheng et al ., 2018; Eddie-Amadi et al, 2025 , Ozoani et al, 2023 ; Ozoani et al, 2025 ). Furthermore, selenium has been shown to regulate cell survival pathways, including those involved in apoptosis and autophagy, thus promoting tissue repair and regeneration (Sahoo et al., 2023 ). However, despite the promising effects of selenium on oxidative stress and organ protection, no report has categorically evaluated the modulatory effect of selenium on the hepato, and nephrotoxic responses to Fe-NTA exposure. This remained unclear to warrant the present investigation. The present study aims to investigate the responses to selenium intake in rats exposed to Fe-NTA, particularly on the modulation hepatic, and renal toxicity in other to explore the potentials of selenium supplementation and it’s impacts on oxidative stress biomarkers, Pro-inflammatory cytokines, and histopathological outcomes of these organs. 2.0. MATERIALS AND METHODS 2.1. Chemicals Chemical used for the study was of analytical grade purchased from Fisher Scientific (UK) and Sigma Aldrich chemical company (St. Louis, MO, USA). 2.2. Preparation of Fe-NTA Preparation of Fe-NTA solution was done by the method of Awai et al. ( 1979 ); Anwar et al, ( 2015 ) as modified by Iqbal et al, ( 2021 ). In brief, ferric nitrate (0.16 mM) solution was mixed with a fourfold molar excess of disodium salt of NTA (0.64 nM). The pH of the solution was adjusted to 7.4 with a sodium bicarbonate solution. The solution was prepared freshly before each protocol. 2.3. Preparation of Selenium Stock solution 0.2mg/ml of selenium was prepared by weighing 43.82mg of Sodium Selenite (Na 2 SeO 3 ), dissolved in 100 mL of distilled water using 50 mL beaker was stir continuously until dissolution was achieved (Akramipour et al, 2019 ). Dilution from the stock solution was done to achieve 0.06mg/ml, 0.08mg/ml and 0.1mg/ml of selenium solutions 2.4. Experimental Design A total of twenty-five (25) male Wistar albino rats were used for the study. Animal were randomly divided into five (5) groups containing ten (5) rats in each group. All animals were acclimatized for two weeks before exposure to 3.0mg/kg of ferric nitrilotriacetate at every other day intraperitoneally (i.p.) for fourteen (14) days except the control (Liebold et al ., 2002), followed by exposure to doses selenium contaminated diet based on selenium Recommended Daily Intake (RDI)(Kipp et al, 2015 ) from day 15–28 daily. The dose of selenium diet was calculated per 100g of feed. The animals were housed in plastic (polypropylene) cages using paddy husk bedding, fed with grower‘s mash and water ad-libitum . The experimental grouped is as follows: Group Normal Saline Ferric nitrilotriacetate (intrapreitoneal (i.p) Selenium (feed contamination) Sacrifice 0.06mg 0.08mg 0.1mg + 29 Group 1 + (0–28) days - - - - + 29 Group 2 + (0–14) days + (15–28) days - - - + 29 Group 3 - + (15–28)days - - + 29 Group 4 - - +(15–28)days - + 29 Group 5 - - - +(15–28)days + 29 2.5. Samples Collection. At the end of the exposure period, the rats were euthanized following cervical dislocation after 24hrs starvation. Blood samples were collected through cardiac puncture using sterile syringe and needle, transferred into a test tube. Tissues (Liver and Kidney) were harvested into sample container sub-merged in ice. 2.6. Blood and Tissue Sample Preparation. The blood samples collected were centrifuged at 3200g revolution for 15minutes, serum was collected for biochemical assay. Wet tissues weighing 1g was homogenized in ice environment with 9ml of 0.1M phosphate buffer (pH 7.4) to obtain 10% tissue homogenates respectively per tissue. Supernatants were collected for biochemical assays. 2.7. Biochemical Assay 2.7.1 Hepatic Parameters Hepatic activity was evaluated on the basis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), Total protein (TP) and alkaline Phosphatase (ALP) adopting the methods of Reitman and Frankel ( 1957 ), Tietz (2015) and Rick et al, ( 1972 ) respectively. 2.7.2 Renal Parameters Renal function was determined with concentration of the following; Creatinine, Blood Urea Nitrogen (BUN), Sodium, chloride, Potassium and uric acid by the methods of Bartels and Bohmer, (1972), Weatherburn ( 1967 ), Maruna (1958) and Trinder ( 1951 ), Skeggs and Hochestrasser (1964), Olarotimi ( 2020 ) and Caraway, 1963 respectively. 2.7.3 Antioxidants Parameters Antioxidants activity was measured on the basis of tissue lipid peroxidation (malondialdehyde (MDA) concentration), tissue reduced glutathione (GSH), tissue catalase activity and superoxide dismutase (SOD) activity according to the methods of Iwetan et al, 2022 , Ellman ( 1959 ) and Misra and Fridovich method (1977) respectively. 2.7.4 . Inflammatory Parameters Determination of proinflammatory cytokines was carried out by the methods of Grellner et al, 2000 , adopted by Ben-Azu et al 2023 the tissue level of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) using ELISA kits and protocols from BioSource (USA). . 2.7.5. Histometric Evaluation Tissue samples from the liver and kidney were collected post-mortem and prepared for histopathological analysis. The examination for the morphological change as done as described by Crocker and Burnett ( 2005 ) and Carlton (1967) on basis of hematoxylin and eosin (H&E). Histological observations were carried out using a light microscope. Data Analysis Data obtained from this study were statistically analyzed and expressed as mean ± standard error of the mean (n = 5), as shown in the corresponding tables and figures. One-way analysis of variance (ANOVA) was employed to assess differences between treatment group means, followed by Tukey’s post hoc test to evaluate the significance of those differences. A 95% confidence level (p < 0.05) was used for all analyses, and distinct superscripts were assigned to indicate statistically significant differences between groups 3.0 RESULTS 3.1. Glutathione level The effect of selenium intake on glutathione (GSH) level in the liver and kidney of rats exposed to Fe-NTA toxicity below; Fig. 1a. Results indicate a significant (P < 0.05) reduction of GSH level in both tissues of rats exposed to Fe-NTA alone when compared to control and all selenium treated groups. Conversely, the effect was a significant reverse in rats exposed to daily intake of selenium when related to Fe-NTA alone group. Values expressed as bar in Mean ± SEM (n = 5). Values in same row with different superscript Significantly differs (p < 0.05) using two ways ANOVA and Tukey’s Multiple comparison test Figure 1a: Effect of Selenium intake on concentration of Reduced Glutathione (GSH) in tissues of Wistar rats expose Fe-NTA Toxicity 3.2. Malondialdehyde (MDA) The effect of selenium intake on Malondialdehyde (MDA) level in the liver and kidney of rats exposed to Fe-NTA toxicity below; Fig. 1b. Malondialdehyde (MDA) level increased Significantly (P < 0.05) in both tissues of rats exposed to 3mg/Kg bw of Fe-NTA alone when compared to control group. A significant(p < 0.05) reduction of MDA in rats exposed to daily intake of selenium was observed in dose depended fashion when related to Fe-NTA alone group. Values expressed as bar in Mean ± SEM (n = 5). Values in same row with different superscript Significantly differs (p < 0.05) using two ways ANOVA and Tukey’s Multiple comparison test Figure 1b Effect of Selenium intake on concentration of Malondialdehyde (MDA) in tissues of Wistar rats expose Fe-NTA Toxicity 3.3 Super Oxide Dismutase (SOD) The effect of selenium intake on Super Oxide Dismutase (SOD) activities in tissues of rats induced with Fe-NTA toxicity is presented below; Fig. 1c. Super Oxide Dismutase (SOD) Significantly (P < 0.05) reduce in tissue of rats exposed to 3mg/Kg bw of Fe-NTA alone when compared to control group. However, SOD activities across groups exposed to selenium demonstrated a significant(p < 0.05) increased in liver and kidney of experimental rats when compared to Fe-NTA alone group. Values expressed as bar in Mean ± SEM (n = 5). Values in same row with different superscript Significantly differs (p < 0.05) using two ways ANOVA and Tukey’s Multiple comparison test Figure 1c Effect of Selenium intake on Superoxide dismutase (SOD) activity in tissues of Wistar rats expose Fe-NTA Toxicity 3.4. Glutathione Transferase (GST) Activity The effect of selenium intake on Glutathione transferase (GST) activities in tissues of rats induced with Fe-NTA toxicity is presented below; Fig. 1d. Glutathione transferase (GST) activities Significantly(P < 0.05) reduce in tissues of rats exposed to 3mg/Kg bw of Fe-NTA alone when compared to control and group of rats administered 0.8mgSe. Meanwhile, when activities of GST was observed in selenium intake groups in both organs, a non-significant effect was seen except rats administered 0.08mgSe that increased significantly(p < 0.05) when compared to other selenium tainted groups and Fe-NTA alone group of rats, Values expressed as bar in Mean ± SEM (n = 5). Values in same row with different superscript Significantly differs (p < 0.05) using two ways ANOVA and Tukey’s Multiple comparison test Figure 1d Effect of Selenium intake on Glutathione Transferase (GST) activity in tissues of Wistar rats expose Fe-NTA Toxicity 3.5. Catalase (CAT) Activity Effect of selenium intake on Catalase (CAT) activities in tissues of rats intoxicated with Fe-NTA is presented below; Fig. 1e. Liver catalase (CAT) activity reduced Significantly (P < 0.05) in groups of rats exposed to Fe-NTA alone, 0.08mgSe and 0.1mgSe when compared to control. However, rats treated with 0.06mgSe showed significant(p < 0.05) elevation of CAT activity in liver when compared to group exposed Fe-NTA and other treatment groups. Similarly, kidney CAT activity of rats significantly(p < 0.05) decreases across all groups when compare to the control group, However, increased significantly(p < 0.05) in group of rats administered 0.06mgSe, 0.08mgSe and 0.1mgSe when effect was related to Fe-NTA alone group of rats. Amongst the selenium treatment groups, rat exposed to oral administration of 0.08mg Se body weight increased significantly in CAT activity compared to other treated with selenium intake. Values expressed as bar in Mean ± SEM (n = 5). Values in same row with different superscript Significantly differs (p < 0.05) using two ways ANOVA and Tukey’s Multiple comparison test Figure 1e Effect of Selenium intake on Catalase Activity in tissues of Wistar rats expose Fe-NTA Toxicity 3.6: Tumor Necrosis Factor-Α Concentration (TNF-α) Effect of selenium intake on Tumor Necrosis factor-α in tissues of rats induced with Fe-NTA toxicity is presented below; Fig. 2a. Tumor Necrosis factor-α concentration significantly(p < 0.05) elevate in tissues exposed to Fe-NTA alone when compared to selenium-tainted groups and the control respectively. Meanwhile, when rats were introduced to selenium Intake, liver tumor Necrosis factor-α (TNF-α) concentration significantly decreased progressively along selenium dosage while kidney TNF-α increased significantly(p < 0.05) along doses of selenium intake when compared to rats exposed to Fe-NTA alone group respectively. Values expressed as bar in Mean ± SEM (n = 5). Values in same row with different superscript Significantly differs (p < 0.05) using two ways ANOVA and Tukey’s Multiple comparison test Figure 2a Effect of Selenium intake on concentration of Tumor Necrosis Factor -α (TNF–α) in tissues of Wistar rats expose Fe-NTA Toxicity 3.8: Interleukin-6 (IL-6) Effect of selenium intake on tissue interleukin-6 (IL-6) level of rats induced with Fe-NTA toxicity is presented below; Fig. 2b. Results show significant (p < 0.05) increase of IL-6 level in tissues of rats exposed to Fe-NTA alone, 0.06mgSe and 0.08mgSe when compared to the control group. Conversely, IL-6 level reduced significantly(p < 0.05) in rats tissues exposed to selenium contaminated diet when related Fe-NTA alone intoxicated group of rats. Values expressed as bar in Mean ± SEM (n = 5). Values in same row with different superscript Significantly differs (p < 0.05) using two ways ANOVA and Tukey’s Multiple comparison test Figure 2b Effect of Selenium intake on concentration of Interleukins − 6 (IL-6) in tissues of Wistar rats expose Fe-NTA Toxicity 3.9: Interleukin-β (IL-β) Effect of selenium intake on tissue interleukin-1β (IL-1β) level of rats induced with Fe-NTA toxicity is presented below; Fig. 2c. There was a significant (p,0.05) increase in kidney IL-1β level of rats induced with Fe-NTA alone when compared to all experimental groups. The effect was reversed significantly(P < 0.05) in kidney of rats exposed to selenium when compared to Fe-NTA alone. Moreso, the liver IL-1β was elevated significantly(p < 0.05) in all investigated groups compared to the control group alone. However, IL-1β in 0.08mgSe and 0.1mgSe level was significantly reduced when compared ferric-alone induced rats Values expressed as bar in Mean ± SEM (n = 5). Values in same row with different superscript Significantly differs (p < 0.05) using two ways ANOVA and Tukey’s Multiple comparison test. Figure 2c Effect of Selenium intake on concentration of Interleukins − 1β (IL-1β) in tissues of Wistar rats expose Fe-NTA Toxicity 3.10: Effect of selenium intake on hepatic and renal activities of rats exposed to Fe-NTA toxicity Table 1 present the effect of selenium intake on hepatic and renal activities of rats exposed to Fe-NTA toxicity. Hepatic indices such as aspartate aminotransferase(AST), Alanine aminotransaminase(ALT) and Total protein(TP) increased significantly(p < 0.05) in serum of rats dosed with 3mg/Kg Fe-NTA alone compared to control, but on the other hand, AST, ALT and TP significantly(p < 0.05) decreased when rats were to daily intake 0.06mgSe, 0.08mgSe and 0.1mgSe compared to Fe-NTA alone, but decrease was non-significant amongst selenium treated groups when compared to other treatment groups. Furthermore, renal indices such as creatinine, Urea, Uric acid, Sodium, Bicarbonate and chlorine concentration significantly(p < 0.05) decreased in groups of rats exposed selenium intake of respective doses; 0.06mgSe, 0.08mgSe and 0.1mgSe compared to Fe-NTA alone. However, serum chloride level of rats on 0.08mgSe intake were non-significant(p < 0.05) compared to Fe-NTA group. On the other hand, potassium concentration increased significantly in groups of rats treated with selenite diets of 0.06mgSe 0.08mgSe and 0.1mgSe when related to both the control and Fe-NTA alone groups. Table 1 Effect of selenium intake on hepatic, and renal activities of rats exposed to Fe-NTA toxicity. Groups/Parameters CTR Fe-NTA Fe-NTA + 0.06mg Se Fe-NTA + 0.08mg Se Fe-NTA + 0.1mg Se HEPATIC AST 155 ± 2.36 a 189 ± 4.13 b 134 ± 0.66 c 139 ± 0.72 cd 142 ± 0.96 d ALT 28.1 ± 0.38 a 38.7 ± 0.38 b 29.2 ± 0.64 ad 29.8 ± 0.84 ad 32.8 ± 0.17 cd TP 1.61 ± 0.04 a 3.55 ± 0.12 b 1.38 ± 0.03 a 1.75 ± 024 cd 2.01 ± 0.04 d RENAL Creatinine 2.01 ± 0.01 a 4.01 ± 0.01 b 2.01 ± 0.01 a 2.05 ± 0.03 a 2.03 ± 0.00 a Urea 103 ± 0.41 a 159 ± 0.55 b 109 ± 0.55 c 125 ± 0.67 d 110 ± 0.72 c Uric acid 3.72 ± 0.09 a 6.17 ± 0.12 b 4.82 ± 0.07 c 3.68 ± 0.23 d 3.83 ± 0.31 c Sodium 155 ± 0.68 a 238 ± 1.12 b 204 ± 0.61 c 171 ± 0.34 d 201 ± 0.40 e Potassium 0.85 ± 0.02 a 0.47 ± 0.04 b 1.31 ± 0.04 c 3.66 ± 0.27 d 4.32 ± 0.13 dc Bicarbonate 18.16 ± 0.49 a 80.0 ± 0.43 b 33.7 ± 0.06 c 46.3 ± 0.15 d 30.9 ± 0.10 e Chloride 122 ± 1.17 a 101 ± 0.43 b 77.3 ± 0.27 c 106.3 ± 0.29 b 87.7 ± 0.35 e Values expressed as Mean ± SEM (n = 5). Values in same row with different alphabets superscript Significantly differs (p < 0.05) using two ways ANOVA and Tukey’s Multiple comparison test. AST = Aspartate Amino transferase, ALT = Alanine Transaminase, TP = Total Protein. . 4.0: Discussion 4.1 Antioxidants Activities Ferric nitrilotriacetate (Fe-NTA), a well-characterized nephrotoxin, causes toxicity primarily through redox cycling and Fenton-type reactions, which generate excessive reactive oxygen species (ROS) and overwhelm the body's endogenous antioxidant defenses (Ramesh and Suresh, 2022 ). Additionally, Achuba and colleagues (2018) demonstrated that dietary selenium supplementation did not affect feed intake. Oxidative stress has been reported to have a crucial role in hepatic and renal abnormalities associated diseases. In this study, iron-induced oxidative stress was evidenced by the obvious and significant (p < 0.05) depletion of cellular antioxidants proteins and particles such as glutathione (GSH), superoxide dismutase (SOD), Catalase and increased malondialdehyde (MDA) levels observed in hepatic and renal tissues (Fig. 1a, 1b, 1c 1d & 1e). Reduced glutathione (GSH), an intracellular antioxidant, is consumed during ROS detoxification to activate increase in MDA concentration, the byproduct of lipid peroxidation and an indicator of cellular membrane damage (Okada et al., 2016 ; Kweki et al, 2018 , Zhao et al ., 2020). From the results, the administration of Fe-NTA initiated systemic tissue oxidative tissue degeneration in predisposed rats. The induced systemic redox influx influenced tissue intoxication that was activated through the redox cycling of iron and enables continuous generation of ROS through Fenton and Haber-Weiss reactions to cause dysregulation of antioxidant defense systems in response to Fe-NTA exposure. see Fig. 1. Obviously, initial exposure may elicit a compensatory increase in enzymatic antioxidants such as superoxide dismutase (SOD), catalase, and glutathione transferases (GST), However, prolonged exposure led to their depletion as presented in Fig. 1, hence the overwhelmed antioxidant response (Ekayoda et al, 2022 ). Additionally, intracellular glutathione (GSH) levels were markedly reduced, further sensitizing cells to oxidative injury and impairing detoxification of lipid peroxides. Selenium diet supplementation, notably at 0.06–0.08 mg, significantly restored GSH concentrations and attenuated MDA accumulation. Our current outcome further affirmed the role of selenium as a cofactor in glutathione peroxidase (GPx) and thioredoxin reductase enzymes essential for neutralizing peroxides and maintaining redox homeostasis (Huang et al., 2021 ; Al-Kunani et al ., 2023). Furthermore, selenium reversed Fe-NTA-induced suppression of enzymatic antioxidants such as superoxide dismutase (SOD), glutathione-S-transferase (GST), and catalase (CAT), albeit in a tissue- and dose-dependent manner. These results support the previous posits of Achuba and colleagues, 2018 that selenium enhances the enzymatic antioxidant defense system, thereby curbing oxidative tissue injury (Surai et al ., 2019; Huang et al., 2021 ). 4.2 Inflammatory Activities Fe-NTA extends beyond oxidative damage per se. Sustained ROS production also activates a variety of pro-inflammatory and pro-survival signaling cascades ( Shahbaz et al, 2023 ), such as NF-κB, MAPKs, and Nrf2 involved in cytoprotective role by upregulating phase II detoxification enzymes (Gado et al, 2023 ). In this present study, witnessed upregulation of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in Fe-NTA-treated rats. This clearly suggest the activation immune inflammatory responses and Fe-NTA interference in nuclear factor kappa B (NF-κB) signaling; an established pathway collecting oxidative stress to inflammation (Gado et al, 2023 ; Jomova et al, 2025 ). In our results, Fe-NTA treatment activated increased expression of (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) associated with cyclin D1 and Bcl-2, which further supports the notion that oxidative stress, hepatocytes and nephron stress signaling are not mutually exclusive but instead cooperatively contribute to transform the tissue(Zhao et al, 2023 ,). Selenium administration to rats effectively suppressed hepatic TNF-α and IL-6 expression (Fig. 2a, 2b & 2c), suggesting selenium immunomodulatory potential and cellular interference to regulate cytokine concentration. However, the less consistent cytokine responses in renal tissue potentially reflect the organ-specific pharmacokinetics or differential redox environments and selenium supplementation. (Kieliszek 2023 ). 4.3. Hepatic Activities The significant elevation of AST and ALT following Fe-NTA exposure (table 2) agreed with previous findings(Kweki et al, 2018 ) as an indication of hepatocellular damage (U. Rehman and Sultana, 2011 ). The elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in tissue of rats exposed to Fe-NTA is a further confirmation of toxic activities by Fe-NTA to initiate hepatocellular membrane degeneration (Ahmed, et al., 2022 ), to permit cytosolic enzymes circulation. ALT, a predominantly liver-specific enzyme (Huang et al , 2023), serves as a sensitive marker of hepatocyte injury. AST, though can also be found in cardiac and skeletal muscle is another marker protein for the confirmation of hepatic damage when elevated in conjunction with ALT (Iwetan et al, 2025 ). Fe-NTA-induced rise in both enzymes, indicates acute hepatic cytolysis, as consistent with prior reports of iron-catalyzed ROS generation to effect lipid peroxidation(U. Rehman and Sultana, 2011 )), particularly with polyunsaturated fatty acids in hepatocyte membranes(U. Rehman and Sultana, 2011 ) This peroxidative assault and compromises membrane integrity, triggering cellular leakage and hepatic protein release(Şahin et al, 2024 ), through the Fenton reaction, wherein Fe²⁺ reacts with hydrogen peroxide (H₂O₂) to produce hydroxyl radicals (•OH) one of the most damaging ROS (ang et al , 2025). Selenium in this present study, did not only normalized the hepatic enzymes activities but also affected total protein (TP) levels, to potentially facilitate timely restoration of hepatocyte function and reduced protein catabolism as well as acute hepatic cytolysis. Selenium’s role in ameliorating oxidative liver injury (Goltyaev and Varlamova, 2023 ). 4.4. Renal activities Table 2 show serum creatinine, urea, and uric acid were significantly elevated by Fe-NTA, to mediate impaired glomerular filtration and renal oxidative damage. Selenium administration show a reversed activities of these indices inconsistent with prior studies (Achuba and colleague, 2018) affirming selenium’s renoprotective efficacy (Sharma et al ., 2017). Partial correction of electrolyte imbalances, particularly for sodium and bicarbonate level. This further gives credence on selenium involvement to improve renal tubular functions in line with (Trigueira et al, 2024 ). Notably, increased potassium levels in selenium-treated groups reflect electron complex interactions in renal ion transport under antioxidant activities and modulation (Hussein et al ,2022). Selenium action is primarily exerted through incorporation into selenoproteins to activate glutathione peroxidases (GPx) and thioredoxin reductases (Chaudière, 2023 ). These enzymes maintain cellular redox balance by reduction of ROS generation from hydrogen peroxide (H₂O₂) and lipid hydroperoxides, thereby preventing excessive oxidative stress linked to aging and diseases such as cancer, cardiovascular disease, and neurodegeneration (Engwa et al, 2022 ). 4.5. Histomorphology In our study, rats exposed to Fe-NTA alone exhibited classic signs of acute hepatocellular injury, including coagulative necrosis(3a-B) notably in the centrilobular zone with preservation of tissue architecture but widespread loss of hepatocyte cords, atrophy, and cytoplasmic degeneration. These conditions are true reflectance of both direct oxidative damage and metabolic failure in zone 3 hepatocytes, and reduced antioxidant capacity compared to periportal (zone 1) hepatocytes (Panday et al, 2022 ). The coagulative necrosis observed is consistent with oxidative collapse of the cytoskeleton and membrane integrity, where cellular proteins are denatured, yet tissue outlines remain preserved, hallmark of ischemic or toxic hepatic injury (Schuermans et al, 2024 ). Additionally, hepatocyte atrophy and degeneration in this region further support the level of sustained oxidative insult, leading to impaired protein synthesis, mitochondrial swelling, and cell shrinkage (Anastasopoulos et al, 2023 ) Dietary supplementation with selenium, a trace element with potent antioxidant function (Acuba and colleague 2018), demonstrated dose-dependent hepatoprotection (Fig. 3 a A-E). Selenium is incorporated into several selenoproteins, most notably glutathione enzymes and thioredoxin reductases, which directly detoxify hydrogen peroxide and lipid hydroperoxides (Chaudière, 2023 ), thus limiting the propagation of free radicals and subsequent membrane lipid damage (Recknagel, et al, 2020 ). At a supplementation level of 0.6 mg Se, show in Fig. 3 a-C, partial hepatoprotection was observed. Histological sections revealed moderate improvement, with a reduction in the extent of necrosis and preservation of some hepatocyte cords. However, residual cellular degeneration and cytoplasmic vacuolization indicated that the antioxidant defense was incompletely restored at this dose. Increasing the selenium supplementation to 0.8 mg produced a more pronounced protective effect (Fig. 3 a-C). The liver histology showed marked attenuation of necrosis, with improved hepatocyte morphology, reconstitution of lobular architecture, and fewer degenerative changes in the centrilobular region(Choi, 2025 ). This suggests that at this dose, selenium may have enhanced glutathione expression or activity to a level sufficient to counteract the Fe-NTA-induced oxidative burden. The most significant histological protection was observed in the group fed with 1.0 mg Se where liver architecture appeared near-normal, with minimal evidence of centrilobular necrosis or hepatocyte atrophy (Fig. 3 a-E). Preservation of hepatocyte cords, absence of cytoplasmic degeneration, and restoration of nuclear integrity strongly support the maximal antioxidant and possibly anti-inflammatory effect at this dosage(Mohammed and Al-Shawi, 2025 ). In addition to upregulating antioxidant enzymes, higher selenium doses may also inhibit NF-κB-mediated inflammatory responses and promote Nrf2 (nuclear factor erythroid 2–related factor 2) activation, enhancing cellular resilience to oxidative injury (Altanam et al., 2025 ) Kidney histology in the Fe-NTA alone group revealed profound architectural distortion, with accentuation of renal cortical and medullary structures, indicating reactive changes secondary to injury. Mesangial cell proliferation was evident within the glomeruli, reflecting an inflammatory and fibrogenic response likely mediated by oxidative stress-induced cytokines, such as TGF-β and IL-6 related factors promoting extracellular matrix expansion (Efiong, et al, 2025 ). The observed ectasia (dilation) of tubular lumens suggests loss of tubular epithelial integrity and compensatory dilation following epithelial cell injury or apoptosis. These findings aligned with previous report of Schelling, ( 2016 ). Tubular atrophy, evidenced by thinning of tubular epithelium and loss of brush border, further indicates chronic oxidative damage and impaired regenerative capacity, these features were also reported in previous study of Cortinovis et al, ( 2024 ). The introduction of selenium supplementation resulted in a marked amelioration of Fe-NTA-induced renal pathology. At a dose of 0.6 mg Se, partial histological improvement was observed (Fig. 3 b-C). While accentuation and mesangial proliferation were still present, the degree of tubular ectasia and atrophy was notably reduced, and patches of normal renal cells were identifiable. This suggests that at lower dose of selenium was sufficient to partially restore redox homeostasis but may not have fully suppressed the inflammatory and fibrotic signaling pathways activated by Fe-NTA. With 0.8 mg Se, the kidneys (Fig. 3 b-D) exhibited improved architecture, with significant reduction in glomerular hypercellularity, attenuation of mesangial expansion, and restoration of normal tubular morphology in large regions. Only minimal ectasia and atrophy were present, and normal renal histological conditions predominated. This indicates an enhanced antioxidant response and potential modulation of transcriptional regulators such as Nrf2, which governs cellular antioxidant (Altanam et al., 2025 ). In the 1.0 mg Se group, the renal histology was essentially indistinguishable from normal controls (Fig. 3 b-E). There was no evidence of mesangial proliferation, ectasia, or tubular atrophy, and the kidneys showed well-preserved glomerular and tubular structures, with abundant normal renal epithelial cells. This further suggests that at this dosage, selenium effectively neutralized Fe-NTA induced oxidative stress, likely by maximizing the activity of GPx and other selenoproteins(Chaudière, 2023 ), thereby halting lipid peroxidation and secondary inflammatory responses (Altanam et al., 2025 ). In addition, selenium may also suppress pro-apoptotic pathways, prserving the mitochondrial integrity and supporting cell survival (Murray et al, 2018 ) 5.0. Conclusion The study posit selenium (Se) supplementation to confers significant protective effects against ferric nitrilotriacetate (Fe-NTA) induced hepato-, and nephrotoxicity in rats, primarily through modulation of oxidative stress, and inflammatory response crucial for immune modulation, and organ histological indices, although, the study sorely support previous established activities of selenium as a potent antioxidant and anti-inflammatory agent, but novelly deviated in the milieu of metal-induced toxicity and for the first time recognized it’s ameliorative potentials on Fe-NTA toxicity. Declarations Conflict of Interest: None declared. Ethics Approval: Study protocol was done in consonance with the guide lines and declarations of Animal Research Ethics (2009) and the World Medical Association (2016) on animal use in bio-medical research and it conformed to the animal rights law in an approval granted by the Faculty of Science ethical committee of Delta State University, Abraka with reference number REL/FOS/2023/11 Funding: No external funding was received for this study, all funds were provided by the authors Author Contribution A CONCEPTUALIZATION OF RESEARCHA.B. WROTE THE MAIN MANUSCRIPT.C.D. DATA ANALYSIS AND PREPARATION OF FIGUREE GENERAL SUPERVISION. Acknowledgement Mr. Andy Ohwokevwo for supporting the research during laboratory analysis References Achuba, F. I., & Obaremi, C. (2018). Effects of selenium fortified diet on inflammatory markers in Wistar albino rats exposed to crude oil. Nigerian Journal of Pharmaceutical and Biomedical Research , 3 (3), 209–216. Adewale, G. G., Olajide, P. A., Omowumi, O. S., Okunlola, D. D., Taiwo, A. M., & Adetuyi, B. O. (2022). Toxicological Significance of the Occurrence of Selenium in Foods. World News of Natural Sciences (WNOFNS) , 44 . Ahmed, A. R., Vun-Sang, S., & Iqbal, M. (2022). Therapeutic role of nitroglycerin against copper-nitrilotriacetate induced hepatic and renal damage. Human & Experimental Toxicology , 41 , 09603271221131312. Akramipour, R., Golpayegani, M. R., Ghasemi, M., Noori, N., & Fattahi, N. (2019). Development of an efficient sample preparation method for the speciation of Se (iv)/Se (vi) and total inorganic selenium in blood of children with acute leukemia. New Journal of Chemistry , 43 (18), 6951–6958. Al Knani, Z. M. I., Al Ashoor, A. S., & Hussein, A. N. Assessment of antioxidant activity in Vaucheria sessilis extracts and their efficacy against isolated Candida spp. from diabetic foot ulcers. Altanam, S. Y., Darwish, N., & Bakillah, A. (2025). Exploring the Interplay of Antioxidants, Inflammation, and Oxidative Stress: Mechanisms, Therapeutic Potential, and Clinical Implications. Diseases , 13 (9), 309. Anastasopoulos, N. A., Charchanti, A. V., Barbouti, A., Mastoridou, E. M., Goussia, A. C., Karampa, A. D., & Glantzounis, G. K. (2023). The role of oxidative stress and cellular senescence in the pathogenesis of metabolic associated fatty liver disease and related hepatocellular carcinoma. Antioxidants , 12 (6), 1269. Anwar, F., Al-Abbasi, F. A., Bhatt, P. C., Ahmad, A., Sethi, N., & Kumar, V. (2015). Umbelliferone β-d-galactopyranoside inhibits chemically induced renal carcinogenesis via alteration of oxidative stress, hyperproliferation and inflammation: possible role of NF-κB. Toxicology Research , 4 (5), 1308–1323. Awai, M., Narasaki, M., Yamanoi, Y., & Seno, S. (1979). Induction of diabetes in animals by parenteral administration of ferric nitrilotriacetate. A model of experimental hemochromatosis. The American Journal of Pathology , 95 (3), 663. Barchielli, G., Capperucci, A., & Tanini, D. (2022). The role of selenium in pathologies: an updated review. Antioxidants , 11 (2), 251.. Bartels, H., Bohmer, M., & Heierli, C. J. C. C. A. (1972). Estimation of serum creatinine without removal of protein. Ben-Azu, B., Uruaka, C. I., Ajayi, A. M., Jarikre, T. A., Nwangwa, K. E., Chilaka, K. C., … Agu, G. O. (2023). Reversal and preventive pleiotropic mechanisms involved in the antipsychotic-like effect of taurine, an essential β-amino acid in ketamine-induced experimental schizophrenia in mice. Neurochemical research , 48 (3), 816–829. Büttner, P., Obradovic, D., Wunderlich, S., Feistritzer, H. J., Holzwirth, E., Lauten, P., … Thiele, H. (2020). Selenoprotein P in myocardial infarction with cardiogenic shock. Shock , 53 (1), 58–62. CARAWAY, W. T., & HALD, P. M. (1963). Uric acid. In Standard methods of clinical chemistry (Vol. 4, pp. 239–247). Elsevier. Chaudière, J. (2023). Biological and catalytic properties of selenoproteins. International Journal of Molecular Sciences , 24 (12), 10109. Choi, J. H. (2025). Histological and Molecular Evaluation of Liver Biopsies: A Practical and Updated Review. International Journal of Molecular Sciences , 26 (16), 7729. Cortinovis, M., Perico, N., & Remuzzi, G. (2024). Tubulointerstitial injury in proteinuric chronic kidney diseases. Frontiers in Medicine , 11 , 1478697. Crocker J, Burnett D (2005) ‘CGH array analysis of human tissues’. The science of laboratory diagnosis, eds 2nd edn. Wiley, pp 523–8 Donia, T., Dabbour, N. M., & Loutfy, S. A. (2023). Hesperidin: advances on resources, biosynthesis pathway, bioavailability, bioactivity, and pharmacology. In Handbook of dietary flavonoids (pp. 1–55). Cham: Springer International Publishing. Eddie-Amadi, B. F., Vangone, R., Guerretti, V., Ozoani, H. A., Okolo, K. O., Awolayeofori, D., … Guerriero, G. (2025). Ovary Metal Toxicity Remediation by Agro-Food Waste: Evidence for a Regulatory Mechanism of Oxidative Stress by Banana (Musa cavendish) Peel Extract. Antioxidants , 14 (9), 1129. Efiong, E. E., Maedler, K., Effa, E., Osuagwu, U. L., Peters, E., Ikebiuro, J. O., … Grallert, H. (2025). Decoding diabetic kidney disease: a comprehensive review of interconnected pathways, molecular mediators, and therapeutic insights. Diabetology & Metabolic Syndrome , 17 (1), 192. Ekayoda, O., Kadiri, H. E., & Ohwokevwo, O. A. (2022). Combined effects of cadmium-and cyanide-contaminated diet on oxidative stress biomarkers in different tissues of rats. Galician Med. J , 29 (4), E202244. El-Demerdash, F. M., Minjal, A. H., El-Sayed, R. A., & Baghdadi, H. H. (2024). Hepatoprotective effect of ethanolic pomegranate peel extract against levofloxacin via suppression of oxidative stress, proinflammation, and apoptosis in male rats. Journal of Medicinal Food , 27 (9), 866–878. Ellman GL (1959). Determination of sulfhydryl group. Arch. Biochem. Biophys., 82: 70–74. Engwa, G. A., Nweke, F. N., & Nkeh-Chungag, B. N. (2022). Free radicals, oxidative stress-related diseases and antioxidant supplementation. Alternative Therapies in Health & Medicine , 28 (1). Gado, F., Ferrario, G., Della Vedova, L., Zoanni, B., Altomare, A., Carini, M., … Baron, G. (2023). Targeting Nrf2 and NF-κB signaling pathways in cancer prevention: The role of apple phytochemicals. Molecules , 28 (3), 1356. Goltyaev, M. V., & Varlamova, E. G. (2023). The role of selenium nanoparticles in the treatment of liver pathologies of various natures. International journal of molecular sciences , 24 (13), 10547. Grellner, W., Georg, T., & Wilske, J. (2000). Quantitative analysis of proinflammatory cytokines (IL-1β, IL-6, TNF-α) in human skin wounds. Forensic science international , 113 (1–3), 251–264. Huang, G., Zang, J., He, L., Zhu, H., Huang, J., Yuan, Z., & Xu, A. (2021). Bioactive nanoenzyme reverses oxidative damage and endoplasmic reticulum stress in neurons under ischemic stroke. ACS nano , 16 (1), 431–452. Huang, H., Qiu, Y., Tang, A., Li, W., Yao, W., Zhong, M., … Zou, T. (2023). The impact of food restriction on liver enzyme levels: a systematic review and meta-analysis. Nutrition Reviews , 81 (8), 939–950. Hussein, J., Farouk, H., & El-Khayat, Z. (2022). Therapeutic Efficacy of Selenium in Management of Hyperhomocytenemia in Cisplatin-Induced Nephrotoxicity. Biomedical and Pharmacology Journal , 15 (4), 1905–1915. Ichipi-Ifukor, P. C., Asagba, S. O., Kweki, G. R., & Nwose, C. (2019). Attenuation of oxidative enzymes induction in palm oil fractions pre-treated cadmium intoxicated rats. Ichipi-Ifukor, P. C., Asagba, S. O., Nwose, C., Mordi, J. C., & Oyem, J. C. (2022). Palm oil extracts protected against cadmium chloride poisoning via inhibition of oxidative stress in rats. Bulletin of the National Research Centre , 46 (1), 5. Iqbal, M., Shah, M. D., Vun-Sang, S., Okazaki, Y., & Okada, S. (2021). The therapeutic potential of curcumin in alleviating N-diethylnitrosamine and iron nitrilotriacetate induced renal cell tumours in mice via inhibition of oxidative stress: Implications for cancer chemoprevention. Biomedicine & Pharmacotherapy , 139 , 111636. Iwetan, B. B., Kweki, G. R., Onobrudu, D. A., Ugochukwu, U., Andy, O. O., Ewhre, L. O., & Obianime, A. W. (2025). Hepatorenal protection of Justicia carnea leaf aqueous extract on sheep red blood cell-induced immunotoxicity in mice. Tropical Journal of Pharmaceutical Research , 24 (5). Iwetan, B. B., Obianime, A. W., Ewhre, L. O., & Kweki, G. R. (2022). The Antioxidant Modulating Properties of Justicia carnea Extract on Sheep Red Blood Cells Immunized Mice. J. Pharmaceut. Res. Int , 34 (33B), 58–74. Jomova, K., Alomar, S. Y., Valko, R., Nepovimova, E., Kuca, K., & Valko, M. (2025). The role of redox-active iron, copper, manganese, and redox-inactive zinc in toxicity, oxidative stress, and human diseases. EXCLI journal , 24 , 880. Kieliszek, M. (2023). Selenium in the prevention of SARS-CoV-2 and other viruses. Biological Trace Element Research , 201 (2), 655–662. Kipp, A. P., Strohm, D., Brigelius-Flohé, R., Schomburg, L., Bechthold, A. E., Leschik-Bonnet, E., & German Nutrition Society (DGE. (2015). Revised reference values for selenium intake. Journal of trace elements in medicine and biology , 32 , 195–199. Kweki, G. R., Ichipi-Ifukor, P. C., & Asagba, S. O. (2018). High caffeine-containing energy drink-induced metabolic stress in rats. Sokoto Journal of Medical Laboratory Science , 3 (3). Leibold, E., Deckardt, K., Mellert, W., Potthoff-Karl, B., Grundler, O., & Jäckh, R. (2002). NTA and Fe (III) NTA: differential patterns of renal toxicity in subchronic studies. Human & Experimental Toxicology , 21 (8), 445–452. Maruna, R. F. L. (1957). Estimation of serum sodium: a critical study of colorimetric methods of estimation and description of a simple photometric method Misra, H. P., & Fridovich, I. (1978). Inhibition of superoxide dismutases by azide. Archives of biochemistry and biophysics , 189 (2), 317–322. Mohammed, R. A., & Al-Shawi, N. N. (2025). Butein mitigates 5-FU-triggered hepatotoxicity via antioxidant, anti-inflammatory, and anti-apoptotic pathways. Toxicology Reports , 102120. Murray, D., Mirzayans, R., & McBride, W. H. (2018). Defenses against pro-oxidant forces-Maintenance of cellular and genomic integrity and longevity. Radiation research , 190 (4), 331–349. Okada, K., Fukui, M., & Zhu, B. T. (2016). Protein disulfide isomerase mediates glutathione depletion-induced cytotoxicity. Biochemical and biophysical research communications , 477 (3), 495–502. Okazaki, Y. (2022). The role of ferric nitrilotriacetate in renal carcinogenesis and cell death: from animal models to clinical implications. Cancers , 14 (6), 1495. Olarotimi, O. J. (2020). Serum electrolyte balance and antioxidant status of broiler chickens fed diets containing varied levels of monosodium glutamate (MSG). Bulletin of the National Research Centre , 44 , 1–7. Olayanju, J. B., Bozic, D., Naidoo, U., & Sadik, O. A. (2024). A comparative review of key isothiocyanates and their health benefits. Nutrients , 16 (6), 757. Olivera, J. (2020). Roles of ZIP14 in Iron Overload-Related Endocrinopathies (Doctoral dissertation, University of Florida). Ozoani, H. A., Ezejiofor, A. N., Orish, C. N., Dokubo, A., Offor, S. J., Uwah, A. F., … Orisakwe, O. E. (2025). Hepatorenal protection of food supplement (Prosopis africana) in rat following metal mixture exposure via alternations in oxido-inflammatory markers. Discover Food , 5 (1), 154. Ozoani, H., Ezejiofor, A. N., Okolo, K. O., Orish, C. N., Cirovic, A., Cirovic, A., & Orisakwe, O. E. (2023). Zinc and selenium attenuate quaternary heavy metal mixture-induced testicular damage via amplification of the antioxidant system, reduction in metal accumulation, inflammatory and apoptotic biomarkers. Toxicological Research , 39 (3), 497–515. Panday, R., Monckton, C. P., & Khetani, S. R. (2022, February). The role of liver zonation in physiology, regeneration, and disease. In Seminars in liver disease (Vol. 42, No. 01, pp. 001–016). Thieme Medical Publishers, Inc Radwan, R. R. (2012). Pharmacological Study of the Effect of Certain Natural Products on Doxorubicin-induced Nephropathy in Rats Exposed to Low Doses of Radiation (No. INIS-EG–391). Faculty of Pharmacy, Cairo University, Cairo (Egypt). Rahbardar, M. G., Farmad, H. C., Hosseinzadeh, H., & Mehri, S. (2021). Protective effects of selenium on acrylamide-induced neurotoxicity and hepatotoxicity in rats. Iranian Journal of Basic Medical Sciences , 24 (8), 1041. Ramesh, R. K., & Suresh, V. (2022). Biomolecules and Pharmacology of Tabernaemontana divaricata (L.) R. Br. ex Roem. & Schult. Bioactives and Pharmacology of Medicinal Plants , 121–137. Recknagel, R. O., Glende, E. A., & Britton, R. S. (2020). Free radical damage and lipid peroxidation. In Hepatotoxicology (pp. 401–436). CRC press. Reitman, S., & Frankel, S. (1957). A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. American journal of clinical pathology , 28 (1), 56–63. Renu, K., Gopalakrishnan, A. V., & Madhyastha, H. (2025). Is periodontitis triggering an inflammatory response in the liver, and does this reaction entail oxidative stress?. Odontology , 113 (3), 889–902. Rick, W., Fritsch, W. P., & Szasz, G. (1972). Fortschritte der klinischen Enzymologie. DMW-Deutsche Medizinische Wochenschrift , 97 (47), 1828–1834. ŞAHIN, I. K., SEZER, C. V., & AYHANCI, A. (2024). THE EFFECTS OF OXIDATIVE STRESS ON CELLULAR STRUCTURES: LIPID PEROXIDATION. OXIDATIVE STRESS AND ANTIOXIDANT DEFENSE SYSTEMS , 15. Sahoo, D. K., Heilmann, R. M., Paital, B., Patel, A., Yadav, V. K., Wong, D., & Jergens, A. E. (2023). Oxidative stress, hormones, and effects of natural antioxidants on intestinal inflammation in inflammatory bowel disease. Frontiers in endocrinology , 14 , 1217165. Saito, Y. (2022). Essential trace element selenium and redox regulation: its metabolism, physiological function, and related diseases. Redox Experimental Medicine , 2022 (1), R149-R158. Schelling, J. R. (2016). Tubular atrophy in the pathogenesis of chronic kidney disease progression. Pediatric nephrology , 31 (5), 693–706. Schuermans, S., Kestens, C., & Marques, P. E. (2024). Systemic mechanisms of necrotic cell debris clearance. Cell Death & Disease , 15 (8), 557. Shahbaz, M., Naeem, H., Imran, M., Ul Hassan, H., Alsagaby, S. A., Al Abdulmonem, W., … Ihsan, A. (2023). Chrysin a promising anticancer agent: recent perspectives. International Journal of Food Properties , 26 (1), 2294–2337. Shimada, B. K., Takayama, N. A., Hallam, K. A., Pjd, S., Yew, J. Y., Alfulaij, N., … Seale, L. A. (2025). A selenomethionine deficient, high-fructose diet does not lead to cardiometabolic disorder in the selenocysteine lyase knockout mice. Journal of Trace Elements in Medicine and Biology , 90 , 127685. Skeggs Jr, L. T., & Hochstrasser, H. (1964). Multiple automatic sequential analysis. Clinical Chemistry , 10 (10), 918–936. Tietz, S., Puthiyaveetil, S., Enlow, H. M., Yarbrough, R., Wood, M., Semchonok, D. A., … Kirchhoff, H. (2015). Functional implications of photosystem II crystal formation in photosynthetic membranes. Journal of Biological Chemistry , 290 (22), 14091–14106. Tilak, J. C., & Devasagayam, T. P. (2006). Oxidative damage to mitochondria. In Oxidative Stress, Disease and Cancer (pp. 85–150). Toyokuni, S., Kong, Y., Cheng, Z., Sato, K., Hayashi, S., Ito, F. and Akatsuka, S. (2020). Carcinogenesis as side effects of iron and oxygen utilization: from the unveiled truth toward ultimate bioengineering. Cancers , 12 (11), 3320. Trigueira, P. D. C., Leal, V. D. O., Cardoso, B. R., Mafra, D., Araujo, M. C., & Stockler-Pinto, M. B. (2024). Selenium supplementation in chronic kidney disease patients undergoing haemodialysis: a systematic review of the effects on plasma selenium, antioxidant and inflammatory markers, immunological parameters and thyroid hormones. Nutrition research reviews , 1–12. Trinder, P. (1951). A rapid method for the determination of sodium in serum. Analyst , 76 (907), 596–599. U. Rehman, M., & Sultana, S. (2011). Attenuation of oxidative stress, inflammation and early markers of tumor promotion by caffeic acid in Fe-NTA exposed kidneys of Wistar rats. Molecular and cellular biochemistry , 357 (1), 115–124. Valko, M. M. H. C. M., Morris, H., & Cronin, M. T. D. (2005). Metals, toxicity and oxidative stress. Current medicinal chemistry , 12 (10), 1161–1208. Wang, D., Zhou, J., Sun, X., & Niu, X. (2025). The Essence of Nature Can be the Simplest (3) Holistic Energy: Extracellular Fenton Reactions of All Cells. Chemistry & Biodiversity , 22 (7), e202500942. Watkins, J. M., Clark, N. M., Song, G., Oliveira, C. C., Mishra, B., Brachova, L., … Jones, A. M. (2021). Phosphorylation dynamics in a flg22-induced, heterotrimeric G-protein dependent signaling network in Arabidopsis thaliana reveals a candidate PP2A phosphatase involved in AtRGS1 trafficking. BioRxiv , 2021-12. Weatherburn, M. (1967). Phenol-hypochlorite reaction for determination of ammonia. Analytical chemistry , 39 (8), 971–974. Zhang, R., Liu, Y., Xing, L., Zhao, N., Zheng, Q., Li, J., & Bao, J. (2018). The protective role of selenium against cadmium-induced hepatotoxicity in laying hens: expression of Hsps and inflammation-related genes and modulation of elements homeostasis. Ecotoxicology and environmental safety , 159 , 205–212. Zhao, J., Zhang, X., Li, Y., Yu, J., Chen, Z., Niu, Y., … Wu, J. (2023). Interorgan communication with the liver: novel mechanisms and therapeutic targets. Frontiers in immunology , 14 , 1314123. Zhou, Z., Wu, H., Yang, R., Xu, A., Zhang, Q., Dong, J. & Sun, M. (2020). GSH depletion liposome adjuvant for augmenting the photothermal immunotherapy of breast cancer. Science advances , 6 (36), eabc4373. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7909439","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":549213439,"identity":"85668036-16af-4cb0-928a-a0fc4cb84493","order_by":0,"name":"Godfrey Rume Kweki","email":"data:image/png;base64,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","orcid":"","institution":"Delta State University","correspondingAuthor":true,"prefix":"","firstName":"Godfrey","middleName":"Rume","lastName":"Kweki","suffix":""},{"id":549213440,"identity":"fbc2c6c5-6d58-4391-8f7e-eb119378a376","order_by":1,"name":"Innocent Ogheneovo Orhonigbe","email":"","orcid":"","institution":"Delta State University","correspondingAuthor":false,"prefix":"","firstName":"Innocent","middleName":"Ogheneovo","lastName":"Orhonigbe","suffix":""},{"id":549213441,"identity":"de455b4d-ed1f-48f2-8153-f0e09fd3719c","order_by":2,"name":"Benedict Bolakponumigha Iwetan","email":"","orcid":"","institution":"Delta State University","correspondingAuthor":false,"prefix":"","firstName":"Benedict","middleName":"Bolakponumigha","lastName":"Iwetan","suffix":""},{"id":549213442,"identity":"ba049dbf-b742-4e99-a8a8-063f55a54c1e","order_by":3,"name":"Micheal Oghenevwhere Oviri","email":"","orcid":"","institution":"Michael and Cicilia University","correspondingAuthor":false,"prefix":"","firstName":"Micheal","middleName":"Oghenevwhere","lastName":"Oviri","suffix":""},{"id":549213443,"identity":"672ef0c7-cbe8-4a53-b975-365527948014","order_by":4,"name":"Joseph Chukwufunaya Mordi","email":"","orcid":"","institution":"Delta State University","correspondingAuthor":false,"prefix":"","firstName":"Joseph","middleName":"Chukwufunaya","lastName":"Mordi","suffix":""}],"badges":[],"createdAt":"2025-10-21 01:38:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7909439/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7909439/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":96708861,"identity":"429fde13-ac88-4f7c-9039-21087bb5c7ef","added_by":"auto","created_at":"2025-11-25 10:05:41","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1283181,"visible":true,"origin":"","legend":"","description":"","filename":"Seleniummanuscript1edited.docx","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/27909412ccf2334468bda846.docx"},{"id":96708888,"identity":"34627744-c663-43ec-9eec-bc191a5de919","added_by":"auto","created_at":"2025-11-25 10:05:58","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":6491,"visible":true,"origin":"","legend":"","description":"","filename":"8b420c1b6831412fbd2857c244bb2234.json","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/ac7c16fcdb8fd6d07af336b9.json"},{"id":96709686,"identity":"1e560793-5e09-48ae-9864-f717e17026fe","added_by":"auto","created_at":"2025-11-25 10:09:31","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":178497,"visible":true,"origin":"","legend":"","description":"","filename":"8b420c1b6831412fbd2857c244bb22341enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/7cad0c0a314d9e4faa55ced9.xml"},{"id":96708355,"identity":"249eed48-3328-493d-af51-312320fc6d75","added_by":"auto","created_at":"2025-11-25 10:01:21","extension":"jpeg","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":106252,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/8efe5bf99eadda0808db6730.jpeg"},{"id":96708526,"identity":"943bebb9-e444-45ca-92d1-08c87d73d5d2","added_by":"auto","created_at":"2025-11-25 10:04:17","extension":"jpeg","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":206543,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage10.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/d8b6514d9a95428b2ab14cb3.jpeg"},{"id":96618859,"identity":"df12b99b-9217-40c0-81af-93319a49e269","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"jpeg","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":101841,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/315aa98d7fa90fadfc619619.jpeg"},{"id":96708662,"identity":"d4601023-087d-4536-9cca-6bfdc45cc2a5","added_by":"auto","created_at":"2025-11-25 10:04:59","extension":"jpeg","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":102721,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/02555ba67ae7f1df1d796759.jpeg"},{"id":96708990,"identity":"c1104867-15cb-4768-9b57-c1267b00b375","added_by":"auto","created_at":"2025-11-25 10:06:58","extension":"jpeg","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":101486,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/b3a0ef12cf5cce04671fa32a.jpeg"},{"id":96708277,"identity":"5bcfee3f-ac4f-43e1-bbe5-f4ed0e116253","added_by":"auto","created_at":"2025-11-25 10:00:03","extension":"jpeg","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":107201,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/7ed1121601c530657411d023.jpeg"},{"id":96708813,"identity":"ca5f78bb-db42-4ec7-ab6f-408d49128491","added_by":"auto","created_at":"2025-11-25 10:05:32","extension":"jpeg","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":96475,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/bb6e6f6043ab8dc15854534e.jpeg"},{"id":96708348,"identity":"70e4eb14-163f-494f-be6b-5e9c69063c1f","added_by":"auto","created_at":"2025-11-25 10:01:16","extension":"jpeg","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":95926,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/d233369ee82d8fc62ae1b64d.jpeg"},{"id":96618872,"identity":"bf4b1983-7e30-45a1-a9d4-a6ae2e9616ce","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"jpeg","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":96995,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage8.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/e67396ca4296bdc735b52c40.jpeg"},{"id":96618865,"identity":"4708df0b-5291-4800-b280-84d72c1d4da8","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"jpeg","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":191993,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage9.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/54b6ff0161c321af5c83627e.jpeg"},{"id":96618874,"identity":"4d58a252-5b6e-45fc-aa86-24e44e4882d9","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"png","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":79417,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/bd876f10a27df1520fdf2e14.png"},{"id":96618867,"identity":"d367099c-b20a-44ab-91ad-8232c7d26fd5","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"png","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":167530,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage10.png","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/31f5cbe3b4713236e2175aea.png"},{"id":96709209,"identity":"bfc31ab9-b9ba-4867-9962-c5f4cb81fbc2","added_by":"auto","created_at":"2025-11-25 10:08:16","extension":"png","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":76525,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/3d5e8ffec994cbd74893ba06.png"},{"id":96709792,"identity":"d1b1634e-cae0-4f59-9cfa-70049b64a2e1","added_by":"auto","created_at":"2025-11-25 10:09:40","extension":"png","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":76493,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/63d3bcf99915e53d1995222c.png"},{"id":96618878,"identity":"057f6143-74e7-47d3-8ed3-c133b3548660","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"png","order_by":17,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":75142,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/84ccecf14507ff6c000ed3a9.png"},{"id":96618876,"identity":"f92a9d87-8c02-4d9b-a3c7-ee080ec77d31","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"png","order_by":18,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":80824,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/a84b9106e128a379be5a4755.png"},{"id":96708337,"identity":"f8988415-7297-4dea-9ad5-61c614fc6e9d","added_by":"auto","created_at":"2025-11-25 10:01:15","extension":"png","order_by":19,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":73681,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/5ff20147546c4ddec7bc0812.png"},{"id":96618871,"identity":"0a55a677-d4a8-41fe-8a95-8e1572a79d00","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"png","order_by":20,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":69268,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/d94aa472b3055e329826522e.png"},{"id":96618881,"identity":"0f0c74c7-fc49-4ab2-a708-053ad60b334d","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"png","order_by":21,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":70215,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/b8c97cbe36b23301b7abfbda.png"},{"id":96618880,"identity":"29a98d81-7eb9-46ef-b321-2cf7c3c87f9b","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"png","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":148988,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/e993c96c211c0592ec669814.png"},{"id":96618882,"identity":"a07f2c46-3656-4d47-8956-cb5a75b4f56a","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"xml","order_by":23,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":175337,"visible":true,"origin":"","legend":"","description":"","filename":"8b420c1b6831412fbd2857c244bb22341structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/13e7c26e360fff353efd1665.xml"},{"id":96618883,"identity":"af36a9ed-94f9-42b2-be8c-e55e2b5b2865","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"html","order_by":24,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":186671,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/f9a73dcf45ac24f6eeddfbd5.html"},{"id":96618849,"identity":"afe32844-d309-4aec-b786-3e8f7d12d993","added_by":"auto","created_at":"2025-11-24 10:39:23","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":106252,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 1a: Effect of Selenium intake on concentration of Reduced Glutathione (GSH) in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\n\u003cp\u003eValues expressed as bar in Mean ± SEM (n=5). Values in same row with different superscript Significantly differs (p\u0026lt;0.05) using two ways ANOVA and Tukey’s Multiple comparison test\u003c/p\u003e","description":"","filename":"image1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/579276749385708e273934e2.jpeg"},{"id":96618848,"identity":"989ea24f-41bf-4054-b532-c7ed8a53fc41","added_by":"auto","created_at":"2025-11-24 10:39:23","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":101841,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig.1b\u003c/strong\u003e: Effect of Selenium intake on concentration of Malondialdehyde (MDA) in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\n\u003cp\u003eValues expressed as bar in Mean ± SEM (n=5). Values in same row with different superscript Significantly differs (p\u0026lt;0.05) using two ways ANOVA and Tukey’s Multiple comparison test\u003c/p\u003e","description":"","filename":"image2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/5aef5e0d4da3225d7a12cbd2.jpeg"},{"id":96710019,"identity":"7e404d63-cfda-409c-89e5-4b76955ccd5c","added_by":"auto","created_at":"2025-11-25 10:09:53","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":102721,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig 1c: \u003c/strong\u003eEffect of Selenium intake on Superoxide dismutase (SOD) activity in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\n\u003cp\u003eValues expressed as bar in Mean ± SEM (n=5). Values in same row with different superscript Significantly differs (p\u0026lt;0.05) using two ways ANOVA and Tukey’s Multiple comparison test\u003c/p\u003e","description":"","filename":"image3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/c51def5e8aa23d8282d4bca3.jpeg"},{"id":96618853,"identity":"1aa822dc-8334-4418-9095-d9b5c03eec32","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":101486,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig 1d: \u003c/strong\u003eEffect of Selenium intake on Glutathione Transferase (GST) activity in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\n\u003cp\u003eValues expressed as bar in Mean ± SEM (n=5). Values in same row with different superscript Significantly differs (p\u0026lt;0.05) using two ways ANOVA and Tukey’s Multiple comparison test\u003c/p\u003e","description":"","filename":"image4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/5d4295115a49f185dd209cfe.jpeg"},{"id":96618856,"identity":"a8f3aa74-30b6-492c-8f13-4257d0d8041c","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":107201,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig.1e: \u003c/strong\u003eEffect of Selenium intake on Catalase Activity in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\n\u003cp\u003eValues expressed as bar in Mean ± SEM (n=5). Values in same row with different superscript Significantly differs (p\u0026lt;0.05) using two ways ANOVA and Tukey’s Multiple comparison test\u003c/p\u003e","description":"","filename":"image5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/cc2708e61b0f62ac007f52a4.jpeg"},{"id":96618858,"identity":"ee05ecad-406c-4074-ab43-16a63aef80e5","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"jpeg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":96475,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig. 2a:\u003c/strong\u003eEffect of Selenium intake on concentration of Tumor Necrosis Factor -α (TNF--α) in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\n\u003cp\u003eValues expressed as bar in Mean ± SEM (n=5). Values in same row with different superscript Significantly differs (p\u0026lt;0.05) using two ways ANOVA and Tukey’s Multiple comparison test\u003c/p\u003e","description":"","filename":"image6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/b62b686dc43a0d29a98b5add.jpeg"},{"id":96708865,"identity":"4cf551b7-abee-41ef-9b44-c27b3471ce89","added_by":"auto","created_at":"2025-11-25 10:05:42","extension":"jpeg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":95926,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig 2b: \u003c/strong\u003eEffect of Selenium intake on concentration of Interleukins -6 (IL-6) in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\n\u003cp\u003eValues expressed as bar in Mean ± SEM (n=5). Values in same row with different superscript Significantly differs (p\u0026lt;0.05) using two ways ANOVA and Tukey’s Multiple comparison test\u003c/p\u003e","description":"","filename":"image7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/a2e7bd3f680ed0165ed226a1.jpeg"},{"id":96618863,"identity":"ad33a31d-e865-4655-bbb4-a0e4258cef9b","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"jpeg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":96995,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig 2c: \u003c/strong\u003eEffect of Selenium intake on concentration of Interleukins -1β (IL-1β) in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\n\u003cp\u003eValues expressed as bar in Mean ± SEM (n=5). Values in same row with different superscript Significantly differs (p\u0026lt;0.05) using two ways ANOVA and Tukey’s Multiple comparison test.\u003c/p\u003e","description":"","filename":"image8.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/d32780a3cf3a345ec6c19063.jpeg"},{"id":96708292,"identity":"43bd71bd-7dd4-4da0-bc30-868b32b51423","added_by":"auto","created_at":"2025-11-25 10:00:28","extension":"jpeg","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":191993,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 3a.: Effect of Selenium intake on histology sections of liver in rats exposed to Fe-NTA toxicity.\u003c/p\u003e","description":"","filename":"image9.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/6801961899660dfb5f8d8715.jpeg"},{"id":96618861,"identity":"412172cc-6a10-457d-bb6c-88ebf2858210","added_by":"auto","created_at":"2025-11-24 10:39:24","extension":"jpeg","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":206543,"visible":true,"origin":"","legend":"\u003cp\u003eFigure 3b. Effect of Selenium intake on histology sections of the Kidney in rats exposed to Fe-NTA toxicity\u003c/p\u003e","description":"","filename":"image10.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/f9b3a1186b9c272302b2666a.jpeg"},{"id":98797049,"identity":"f89cb7dd-d35a-4424-81ed-3b92763a0993","added_by":"auto","created_at":"2025-12-22 12:57:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2399418,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7909439/v1/872ffcfa-d0ac-4775-bb38-682ce80664ed.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eSelenium Intake Modulates Hepato and Nephrotoxic Responses in Rats Exposed to Ferric Nitrilotriacetate (Fe-NTA)\u003c/p\u003e","fulltext":[{"header":"1.0. INTRODUCTION","content":"\u003cp\u003eAmong the diverse toxicological models used to explore chemical-induced organ toxicity, Ferric Nitrilotriacetate (Fe-NTA) has emerged as a potent inducer of oxidative stress, particularly in the kidneys and liver with severe comorbid effects in brain, testicle, and prostate. (Olivera, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Okazaki, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Fe-NTA is a nephrotoxic agent, known for inducing acute renal injury via the Fenton chemistry mediation, which generates highly reactive hydroxyl radicals that damage lipids, proteins, and nucleic acids, ultimately leading to cellular dysfunction, inflammation, and apoptosis (Valko et al., \u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e2005\u003c/span\u003e, Tilak and Devasagayam, \u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e2006\u003c/span\u003e; Toyokuni et al, \u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Primarily, Fe-NTA, is associated with nephrotoxicity. Several studies have also demonstrated its capacity to induce widespread systemic damage, including hepatic and hematological alterations, due to its profound effects on oxidative pathways and cellular integrity (Radwan, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Okazaki, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Donia et al, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). The liver, as the primary detoxification organ is specifically susceptible to oxidative damage, which manifests as hepatocellular necrosis, fibrosis, and inflammation (Kweki et al., \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2018\u003c/span\u003e, Ichipi-Ifukor et al, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Similarly, Fe-NTA exposure results in hematological abnormalities such as reduced red and white blood cell counts, hemolysis, and immune suppression, further complicating its toxicological profile (Olivera, \u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Watkins et al, \u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; El-Demerdash et al, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAs a trace and essential element (Rahbardar et al, \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e2021\u003c/span\u003e ), selenium plays an essential role in maintaining cellular homeostasis through its incorporation into selenoproteins that function as antioxidants, enzymes in thyroid hormone metabolism, and modulators of immune responses (Achuba and Obaremi, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Antioxidative properties of this element is largely attributed to its ability to interacts with antioxidant enzymes of glutathione cycle (Olayanju et al, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Selenoprotein P, that are involved in neutralizing reactive oxygen species (ROS) and reducing oxidative stress (B\u0026uuml;ttner et al, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2020\u003c/span\u003e. Saito, \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Chaudi\u0026egrave;re, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Emerging evidence in recent decades, shows that selenium has garnered significant attention for its potential in mitigating oxidative stress-induced damage in different organs, especially under conditions of chemical exposure or environmental toxicity (Renu et al, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). However, the deficiency of selenium can be implicative in a range of diseases, including cancer, cardiovascular disease, and immune dysfunction (Shimada et al, \u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e2025\u003c/span\u003e, Barchielli, 2022), when consumed in excess. Symptoms such as selenosis, gastrointestinal distress, and neurological impairments are well documented in link with selenium (Barchielli et al, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Adewale et al, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). This dose-dependent relationship between selenium\u0026rsquo;s beneficial and toxic effects underscores the importance of understanding its role under different exposure conditions.\u003c/p\u003e\u003cp\u003eFurther evidences have also highlighted the potential of selenium supplementation to modulate oxidative stress and reduce toxicity associated with various environmental and chemical insults(Achuba and Obaremi, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2018\u003c/span\u003e), including heavy metal exposure (Ichipi-ifukor et al, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Selenium\u0026rsquo;s ability to enhance antioxidant defense systems has been postulated to counteract the oxidative damage caused by ROS and mitigate the downstream effects of lipid peroxidation, protein oxidation, and DNA damage. However, reports have demonstrated that selenium can alleviate kidney and liver damage induced by toxins such as cadmium, lead, and mercury by restoring antioxidant enzyme activity and reducing pro-inflammatory cytokine levels (Zheng \u003cem\u003eet al\u003c/em\u003e., 2018; Eddie-Amadi et al, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2025\u003c/span\u003e, Ozoani et al, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Ozoani et al, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Furthermore, selenium has been shown to regulate cell survival pathways, including those involved in apoptosis and autophagy, thus promoting tissue repair and regeneration (Sahoo et al., \u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). However, despite the promising effects of selenium on oxidative stress and organ protection, no report has categorically evaluated the modulatory effect of selenium on the hepato, and nephrotoxic responses to Fe-NTA exposure. This remained unclear to warrant the present investigation.\u003c/p\u003e\u003cp\u003eThe present study aims to investigate the responses to selenium intake in rats exposed to Fe-NTA, particularly on the modulation hepatic, and renal toxicity in other to explore the potentials of selenium supplementation and it\u0026rsquo;s impacts on oxidative stress biomarkers, Pro-inflammatory cytokines, and histopathological outcomes of these organs.\u003c/p\u003e"},{"header":"2.0. MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1. Chemicals\u003c/h2\u003e\u003cp\u003eChemical used for the study was of analytical grade purchased from Fisher Scientific (UK) and Sigma Aldrich chemical company (St. Louis, MO, USA).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2. Preparation of Fe-NTA\u003c/h2\u003e\u003cp\u003ePreparation of Fe-NTA solution was done by the method of Awai et al. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e1979\u003c/span\u003e); Anwar et al, (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2015\u003c/span\u003e) as modified by Iqbal et al, (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). In brief, ferric nitrate (0.16 mM) solution was mixed with a fourfold molar excess of disodium salt of NTA (0.64 nM). The pH of the solution was adjusted to 7.4 with a sodium bicarbonate solution. The solution was prepared freshly before each protocol.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3. Preparation of Selenium\u003c/h2\u003e\u003cp\u003eStock solution 0.2mg/ml of selenium was prepared by weighing 43.82mg of Sodium Selenite (Na\u003csub\u003e2\u003c/sub\u003eSeO\u003csub\u003e3\u003c/sub\u003e), dissolved in 100 mL of distilled water using 50 mL beaker was stir continuously until dissolution was achieved (Akramipour et al, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Dilution from the stock solution was done to achieve 0.06mg/ml, 0.08mg/ml and 0.1mg/ml of selenium solutions\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4. Experimental Design\u003c/h2\u003e\u003cp\u003eA total of twenty-five (25) male Wistar albino rats were used for the study. Animal were randomly divided into five (5) groups containing ten (5) rats in each group. All animals were acclimatized for two weeks before exposure to 3.0mg/kg of ferric nitrilotriacetate at every other day intraperitoneally (i.p.) for fourteen (14) days except the control (Liebold \u003cem\u003eet al\u003c/em\u003e., 2002), followed by exposure to doses selenium contaminated diet based on selenium Recommended Daily Intake (RDI)(Kipp et al, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2015\u003c/span\u003e) from day 15\u0026ndash;28 daily. The dose of selenium diet was calculated per 100g of feed. The animals were housed in plastic (polypropylene) cages using paddy husk bedding, fed with grower\u0026lsquo;s mash and water \u003cem\u003ead-libitum\u003c/em\u003e. The experimental grouped is as follows:\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNormal Saline\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFerric nitrilotriacetate (intrapreitoneal (i.p)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e\u003cp\u003eSelenium (feed contamination)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSacrifice\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.06mg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.08mg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.1mg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u0026thinsp;29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e+ (0\u0026ndash;28) days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u0026thinsp;29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e+ (0\u0026ndash;14) days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e+ (15\u0026ndash;28) days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u0026thinsp;29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e+ (15\u0026ndash;28)days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u0026thinsp;29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e+(15\u0026ndash;28)days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u0026thinsp;29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup 5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e+(15\u0026ndash;28)days\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+\u0026thinsp;29\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e2.5. Samples Collection.\u003c/h2\u003e\u003cp\u003eAt the end of the exposure period, the rats were euthanized following cervical dislocation after 24hrs starvation. Blood samples were collected through cardiac puncture using sterile syringe and needle, transferred into a test tube. Tissues (Liver and Kidney) were harvested into sample container sub-merged in ice.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e2.6. Blood and Tissue Sample Preparation.\u003c/h2\u003e\u003cp\u003eThe blood samples collected were centrifuged at 3200g revolution for 15minutes, serum was collected for biochemical assay. Wet tissues weighing 1g was homogenized in ice environment with 9ml of 0.1M phosphate buffer (pH 7.4) to obtain 10% tissue homogenates respectively per tissue. Supernatants were collected for biochemical assays.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e2.7. Biochemical Assay\u003c/h2\u003e\u003cdiv id=\"Sec10\" class=\"Section3\"\u003e\u003ch2\u003e2.7.1 Hepatic Parameters\u003c/h2\u003e\u003cp\u003eHepatic activity was evaluated on the basis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), Total protein (TP) and alkaline Phosphatase (ALP) adopting the methods of Reitman and Frankel (\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e1957\u003c/span\u003e), Tietz (2015) and Rick et al, (\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e1972\u003c/span\u003e) respectively.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section3\"\u003e\u003ch2\u003e2.7.2 Renal Parameters\u003c/h2\u003e\u003cp\u003eRenal function was determined with concentration of the following; Creatinine, Blood Urea Nitrogen (BUN), Sodium, chloride, Potassium and uric acid by the methods of Bartels and Bohmer, (1972), Weatherburn (\u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e1967\u003c/span\u003e), Maruna (1958) and Trinder (\u003cspan citationid=\"CR73\" class=\"CitationRef\"\u003e1951\u003c/span\u003e), Skeggs and Hochestrasser (1964), Olarotimi (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) and Caraway, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e1963\u003c/span\u003e respectively.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section3\"\u003e\u003ch2\u003e2.7.3 Antioxidants Parameters\u003c/h2\u003e\u003cp\u003eAntioxidants activity was measured on the basis of tissue lipid peroxidation (malondialdehyde (MDA) concentration), tissue reduced glutathione (GSH), tissue catalase activity and superoxide dismutase (SOD) activity according to the methods of Iwetan et al, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2022\u003c/span\u003e, Ellman (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e1959\u003c/span\u003e) and Misra and Fridovich method (1977) respectively.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section3\"\u003e\u003ch2\u003e\u003cb\u003e2.7.4\u003c/b\u003e. \u003cb\u003eInflammatory Parameters\u003c/b\u003e\u003c/h2\u003e\u003cp\u003eDetermination of proinflammatory cytokines was carried out by the methods of Grellner et al, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2000\u003c/span\u003e, adopted by Ben-Azu et al \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2023\u003c/span\u003e the tissue level of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) using ELISA kits and protocols from BioSource (USA). .\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section3\"\u003e\u003ch2\u003e2.7.5. Histometric Evaluation\u003c/h2\u003e\u003cp\u003eTissue samples from the liver and kidney were collected post-mortem and prepared for histopathological analysis. The examination for the morphological change as done as described by Crocker and Burnett (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2005\u003c/span\u003e) and Carlton (1967) on basis of hematoxylin and eosin (H\u0026amp;E). Histological observations were carried out using a light microscope.\u003c/p\u003e\u003cp\u003e\u003cb\u003eData Analysis\u003c/b\u003e\u003c/p\u003e\u003cp\u003eData obtained from this study were statistically analyzed and expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard error of the mean (n\u0026thinsp;=\u0026thinsp;5), as shown in the corresponding tables and figures. One-way analysis of variance (ANOVA) was employed to assess differences between treatment group means, followed by Tukey\u0026rsquo;s post hoc test to evaluate the significance of those differences. A 95% confidence level (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) was used for all analyses, and distinct superscripts were assigned to indicate statistically significant differences between groups\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"3.0 RESULTS","content":"\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003e3.1. Glutathione level\u003c/h2\u003e\u003cp\u003eThe effect of selenium intake on glutathione (GSH) level in the liver and kidney of rats exposed to Fe-NTA toxicity below; Fig.\u0026nbsp;1a. Results indicate a significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) reduction of GSH level in both tissues of rats exposed to Fe-NTA alone when compared to control and all selenium treated groups. Conversely, the effect was a significant reverse in rats exposed to daily intake of selenium when related to Fe-NTA alone group.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eValues expressed as bar in Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM (n\u0026thinsp;=\u0026thinsp;5). Values in same row with different superscript Significantly differs (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) using two ways ANOVA and Tukey\u0026rsquo;s Multiple comparison test\u003c/p\u003e\u003cp\u003eFigure 1a: Effect of Selenium intake on concentration of Reduced Glutathione (GSH) in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003e3.2. Malondialdehyde (MDA)\u003c/h2\u003e\u003cp\u003eThe effect of selenium intake on Malondialdehyde (MDA) level in the liver and kidney of rats exposed to Fe-NTA toxicity below; Fig.\u0026nbsp;1b. Malondialdehyde (MDA) level increased Significantly (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in both tissues of rats exposed to 3mg/Kg bw of Fe-NTA alone when compared to control group. A significant(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) reduction of MDA in rats exposed to daily intake of selenium was observed in dose depended fashion when related to Fe-NTA alone group.\u003c/p\u003e\u003cp\u003eValues expressed as bar in Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM (n\u0026thinsp;=\u0026thinsp;5). Values in same row with different superscript Significantly differs (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) using two ways ANOVA and Tukey\u0026rsquo;s Multiple comparison test\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFigure\u0026nbsp;1b\u003c/strong\u003e\u003cp\u003eEffect of Selenium intake on concentration of Malondialdehyde (MDA) in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Super Oxide Dismutase (SOD)\u003c/h2\u003e\u003cp\u003eThe effect of selenium intake on Super Oxide Dismutase (SOD) activities in tissues of rats induced with Fe-NTA toxicity is presented below; Fig.\u0026nbsp;1c. Super Oxide Dismutase (SOD) Significantly (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) reduce in tissue of rats exposed to 3mg/Kg bw of Fe-NTA alone when compared to control group. However, SOD activities across groups exposed to selenium demonstrated a significant(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) increased in liver and kidney of experimental rats when compared to Fe-NTA alone group.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eValues expressed as bar in Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM (n\u0026thinsp;=\u0026thinsp;5). Values in same row with different superscript Significantly differs (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) using two ways ANOVA and Tukey\u0026rsquo;s Multiple comparison test\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFigure\u0026nbsp;1c\u003c/strong\u003e\u003cp\u003eEffect of Selenium intake on Superoxide dismutase (SOD) activity in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003e3.4. Glutathione Transferase (GST) Activity\u003c/h2\u003e\u003cp\u003eThe effect of selenium intake on Glutathione transferase (GST) activities in tissues of rats induced with Fe-NTA toxicity is presented below; Fig.\u0026nbsp;1d. Glutathione transferase (GST) activities Significantly(P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) reduce in tissues of rats exposed to 3mg/Kg bw of Fe-NTA alone when compared to control and group of rats administered 0.8mgSe. Meanwhile, when activities of GST was observed in selenium intake groups in both organs, a non-significant effect was seen except rats administered 0.08mgSe that increased significantly(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) when compared to other selenium tainted groups and Fe-NTA alone group of rats,\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eValues expressed as bar in Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM (n\u0026thinsp;=\u0026thinsp;5). Values in same row with different superscript Significantly differs (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) using two ways ANOVA and Tukey\u0026rsquo;s Multiple comparison test\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFigure\u0026nbsp;1d\u003c/strong\u003e\u003cp\u003eEffect of Selenium intake on Glutathione Transferase (GST) activity in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003e3.5. Catalase (CAT) Activity\u003c/h2\u003e\u003cp\u003eEffect of selenium intake on Catalase (CAT) activities in tissues of rats intoxicated with Fe-NTA is presented below; Fig.\u0026nbsp;1e. Liver catalase (CAT) activity reduced Significantly (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in groups of rats exposed to Fe-NTA alone, 0.08mgSe and 0.1mgSe when compared to control. However, rats treated with 0.06mgSe showed significant(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) elevation of CAT activity in liver when compared to group exposed Fe-NTA and other treatment groups. Similarly, kidney CAT activity of rats significantly(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) decreases across all groups when compare to the control group, However, increased significantly(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in group of rats administered 0.06mgSe, 0.08mgSe and 0.1mgSe when effect was related to Fe-NTA alone group of rats. Amongst the selenium treatment groups, rat exposed to oral administration of 0.08mg Se body weight increased significantly in CAT activity compared to other treated with selenium intake.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eValues expressed as bar in Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM (n\u0026thinsp;=\u0026thinsp;5). Values in same row with different superscript Significantly differs (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) using two ways ANOVA and Tukey\u0026rsquo;s Multiple comparison test\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFigure\u0026nbsp;1e\u003c/strong\u003e\u003cp\u003eEffect of Selenium intake on Catalase Activity in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\u003ch2\u003e3.6: Tumor Necrosis Factor-Α Concentration (TNF-α)\u003c/h2\u003e\u003cp\u003eEffect of selenium intake on Tumor Necrosis factor-α in tissues of rats induced with Fe-NTA toxicity is presented below; Fig.\u0026nbsp;2a. Tumor Necrosis factor-α concentration significantly(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) elevate in tissues exposed to Fe-NTA alone when compared to selenium-tainted groups and the control respectively. Meanwhile, when rats were introduced to selenium Intake, liver tumor Necrosis factor-α (TNF-α) concentration significantly decreased progressively along selenium dosage while kidney TNF-α increased significantly(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) along doses of selenium intake when compared to rats exposed to Fe-NTA alone group respectively.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eValues expressed as bar in Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM (n\u0026thinsp;=\u0026thinsp;5). Values in same row with different superscript Significantly differs (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) using two ways ANOVA and Tukey\u0026rsquo;s Multiple comparison test\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFigure\u0026nbsp;2a\u003c/strong\u003e\u003cp\u003eEffect of Selenium intake on concentration of Tumor Necrosis Factor -α (TNF\u0026ndash;α) in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\u003ch2\u003e3.8: Interleukin-6 (IL-6)\u003c/h2\u003e\u003cp\u003eEffect of selenium intake on tissue interleukin-6 (IL-6) level of rats induced with Fe-NTA toxicity is presented below; Fig.\u0026nbsp;2b. Results show significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) increase of IL-6 level in tissues of rats exposed to Fe-NTA alone, 0.06mgSe and 0.08mgSe when compared to the control group. Conversely, IL-6 level reduced significantly(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in rats tissues exposed to selenium contaminated diet when related Fe-NTA alone intoxicated group of rats.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eValues expressed as bar in Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM (n\u0026thinsp;=\u0026thinsp;5). Values in same row with different superscript Significantly differs (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) using two ways ANOVA and Tukey\u0026rsquo;s Multiple comparison test\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFigure\u0026nbsp;2b\u003c/strong\u003e\u003cp\u003eEffect of Selenium intake on concentration of Interleukins \u0026minus;\u0026thinsp;6 (IL-6) in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec23\" class=\"Section2\"\u003e\u003ch2\u003e3.9: Interleukin-β (IL-β)\u003c/h2\u003e\u003cp\u003eEffect of selenium intake on tissue interleukin-1β (IL-1β) level of rats induced with Fe-NTA toxicity is presented below; Fig.\u0026nbsp;2c. There was a significant (p,0.05) increase in kidney IL-1β level of rats induced with Fe-NTA alone when compared to all experimental groups. The effect was reversed significantly(P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in kidney of rats exposed to selenium when compared to Fe-NTA alone. Moreso, the liver IL-1β was elevated significantly(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in all investigated groups compared to the control group alone. However, IL-1β in 0.08mgSe and 0.1mgSe level was significantly reduced when compared ferric-alone induced rats\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eValues expressed as bar in Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM (n\u0026thinsp;=\u0026thinsp;5). Values in same row with different superscript Significantly differs (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) using two ways ANOVA and Tukey\u0026rsquo;s Multiple comparison test.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFigure\u0026nbsp;2c\u003c/strong\u003e\u003cp\u003eEffect of Selenium intake on concentration of Interleukins \u0026minus;\u0026thinsp;1β (IL-1β) in tissues of Wistar rats expose Fe-NTA Toxicity\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec24\" class=\"Section2\"\u003e\u003ch2\u003e3.10: Effect of selenium intake on hepatic and renal activities of rats exposed to Fe-NTA toxicity\u003c/h2\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e present the effect of selenium intake on hepatic and renal activities of rats exposed to Fe-NTA toxicity. Hepatic indices such as aspartate aminotransferase(AST), Alanine aminotransaminase(ALT) and Total protein(TP) increased significantly(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in serum of rats dosed with 3mg/Kg Fe-NTA alone compared to control, but on the other hand, AST, ALT and TP significantly(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) decreased when rats were to daily intake 0.06mgSe, 0.08mgSe and 0.1mgSe compared to Fe-NTA alone, but decrease was non-significant amongst selenium treated groups when compared to other treatment groups.\u003c/p\u003e\u003cp\u003eFurthermore, renal indices such as creatinine, Urea, Uric acid, Sodium, Bicarbonate and chlorine concentration significantly(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) decreased in groups of rats exposed selenium intake of respective doses; 0.06mgSe, 0.08mgSe and 0.1mgSe compared to Fe-NTA alone. However, serum chloride level of rats on 0.08mgSe intake were non-significant(p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) compared to Fe-NTA group. On the other hand, potassium concentration increased significantly in groups of rats treated with selenite diets of 0.06mgSe 0.08mgSe and 0.1mgSe when related to both the control and Fe-NTA alone groups.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eEffect of selenium intake on hepatic, and renal activities of rats exposed to Fe-NTA toxicity.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroups/Parameters\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCTR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFe-NTA\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eFe-NTA\u0026thinsp;+\u0026thinsp;0.06mg Se\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFe-NTA\u0026thinsp;+\u0026thinsp;0.08mg\u003c/p\u003e\u003cp\u003eSe\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eFe-NTA\u0026thinsp;+\u0026thinsp;0.1mg Se\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003eHEPATIC\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAST\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e155\u0026thinsp;\u0026plusmn;\u0026thinsp;2.36\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e189\u0026thinsp;\u0026plusmn;\u0026thinsp;4.13\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e134\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e139\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003csup\u003ecd\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e142\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eALT\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e29.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003csup\u003ead\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e29.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.84\u003csup\u003ead\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e32.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003csup\u003ecd\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.75\u0026thinsp;\u0026plusmn;\u0026thinsp;024\u003csup\u003ecd\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRENAL\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCreatinine\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.01\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.05\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUrea\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e103\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e159\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e109\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e125\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e110\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUric acid\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSodium\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e155\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e238\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e204\u0026thinsp;\u0026plusmn;\u0026thinsp;0.61\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e171\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e201\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePotassium\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.66\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003csup\u003edc\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBicarbonate\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e80.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e33.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e46.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e30.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChloride\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e122\u0026thinsp;\u0026plusmn;\u0026thinsp;1.17\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e101\u0026thinsp;\u0026plusmn;\u0026thinsp;0.43\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e77.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e106.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e87.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.35\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eValues expressed as Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM (n\u0026thinsp;=\u0026thinsp;5). Values in same row with different alphabets superscript Significantly differs (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) using two ways ANOVA and Tukey\u0026rsquo;s Multiple comparison test. \u003cb\u003eAST\u003c/b\u003e\u0026thinsp;=\u0026thinsp;Aspartate Amino transferase, ALT\u0026thinsp;=\u0026thinsp;Alanine Transaminase, TP\u0026thinsp;=\u0026thinsp;Total Protein.\u003c/p\u003e\u003cp\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"4.0: Discussion","content":"\u003cdiv id=\"Sec26\" class=\"Section2\"\u003e\u003ch2\u003e4.1 Antioxidants Activities\u003c/h2\u003e\u003cp\u003eFerric nitrilotriacetate (Fe-NTA), a well-characterized nephrotoxin, causes toxicity primarily through redox cycling and Fenton-type reactions, which generate excessive reactive oxygen species (ROS) and overwhelm the body's endogenous antioxidant defenses (Ramesh and Suresh, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Additionally, Achuba and colleagues (2018) demonstrated that dietary selenium supplementation did not affect feed intake. Oxidative stress has been reported to have a crucial role in hepatic and renal abnormalities associated diseases. In this study, iron-induced oxidative stress was evidenced by the obvious and significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) depletion of cellular antioxidants proteins and particles such as glutathione (GSH), superoxide dismutase (SOD), Catalase and increased malondialdehyde (MDA) levels observed in hepatic and renal tissues (Fig.\u0026nbsp;1a, 1b, 1c 1d \u0026amp; 1e). Reduced glutathione (GSH), an intracellular antioxidant, is consumed during ROS detoxification to activate increase in MDA concentration, the byproduct of lipid peroxidation and an indicator of cellular membrane damage (Okada et al., \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Kweki et al, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2018\u003c/span\u003e, Zhao \u003cem\u003eet al\u003c/em\u003e., 2020). From the results, the administration of Fe-NTA initiated systemic tissue oxidative tissue degeneration in predisposed rats. The induced systemic redox influx influenced tissue intoxication that was activated through the redox cycling of iron and enables continuous generation of ROS through Fenton and Haber-Weiss reactions to cause dysregulation of antioxidant defense systems in response to Fe-NTA exposure. see Fig.\u0026nbsp;1. Obviously, initial exposure may elicit a compensatory increase in enzymatic antioxidants such as superoxide dismutase (SOD), catalase, and glutathione transferases (GST), However, prolonged exposure led to their depletion as presented in Fig.\u0026nbsp;1, hence the overwhelmed antioxidant response (Ekayoda et al, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Additionally, intracellular glutathione (GSH) levels were markedly reduced, further sensitizing cells to oxidative injury and impairing detoxification of lipid peroxides. Selenium diet supplementation, notably at 0.06\u0026ndash;0.08 mg, significantly restored GSH concentrations and attenuated MDA accumulation. Our current outcome further affirmed the role of selenium as a cofactor in glutathione peroxidase (GPx) and thioredoxin reductase enzymes essential for neutralizing peroxides and maintaining redox homeostasis (Huang et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Al-Kunani \u003cem\u003eet al\u003c/em\u003e., 2023). Furthermore, selenium reversed Fe-NTA-induced suppression of enzymatic antioxidants such as superoxide dismutase (SOD), glutathione-S-transferase (GST), and catalase (CAT), albeit in a tissue- and dose-dependent manner. These results support the previous posits of Achuba and colleagues, 2018 that selenium enhances the enzymatic antioxidant defense system, thereby curbing oxidative tissue injury (Surai \u003cem\u003eet al\u003c/em\u003e., 2019; Huang et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec27\" class=\"Section2\"\u003e\u003ch2\u003e4.2 Inflammatory Activities\u003c/h2\u003e\u003cp\u003eFe-NTA extends beyond oxidative damage per se. Sustained ROS production also activates a variety of pro-inflammatory and pro-survival signaling cascades \u003cb\u003e(\u003c/b\u003eShahbaz et al, \u003cspan citationid=\"CR66\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), such as NF-κB, MAPKs, and Nrf2 involved in cytoprotective role by upregulating phase II detoxification enzymes (Gado et al, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). In this present study, witnessed upregulation of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in Fe-NTA-treated rats. This clearly suggest the activation immune inflammatory responses and Fe-NTA interference in nuclear factor kappa B (NF-κB) signaling; an established pathway collecting oxidative stress to inflammation (Gado et al, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Jomova et al, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). In our results, Fe-NTA treatment activated increased expression of (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) associated with cyclin D1 and Bcl-2, which further supports the notion that oxidative stress, hepatocytes and nephron stress signaling are not mutually exclusive but instead cooperatively contribute to transform the tissue(Zhao et al, \u003cspan citationid=\"CR80\" class=\"CitationRef\"\u003e2023\u003c/span\u003e,). Selenium administration to rats effectively suppressed hepatic TNF-α and IL-6 expression (Fig.\u0026nbsp;2a, 2b \u0026amp; 2c), suggesting selenium immunomodulatory potential and cellular interference to regulate cytokine concentration. However, the less consistent cytokine responses in renal tissue potentially reflect the organ-specific pharmacokinetics or differential redox environments and selenium supplementation. (Kieliszek \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec28\" class=\"Section2\"\u003e\u003ch2\u003e4.3. Hepatic Activities\u003c/h2\u003e\u003cp\u003eThe significant elevation of AST and ALT following Fe-NTA exposure (table 2) agreed with previous findings(Kweki et al, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2018\u003c/span\u003e) as an indication of hepatocellular damage (U. Rehman and Sultana, \u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). The elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in tissue of rats exposed to Fe-NTA is a further confirmation of toxic activities by Fe-NTA to initiate hepatocellular membrane degeneration (Ahmed, et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), to permit cytosolic enzymes circulation. ALT, a predominantly liver-specific enzyme (Huang \u003cem\u003eet al\u003c/em\u003e, 2023), serves as a sensitive marker of hepatocyte injury. AST, though can also be found in cardiac and skeletal muscle is another marker protein for the confirmation of hepatic damage when elevated in conjunction with ALT (Iwetan et al, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Fe-NTA-induced rise in both enzymes, indicates acute hepatic cytolysis, as consistent with prior reports of iron-catalyzed ROS generation to effect lipid peroxidation(U. Rehman and Sultana, \u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e2011\u003c/span\u003e)), particularly with polyunsaturated fatty acids in hepatocyte membranes(U. Rehman and Sultana, \u003cspan citationid=\"CR74\" class=\"CitationRef\"\u003e2011\u003c/span\u003e) This peroxidative assault and compromises membrane integrity, triggering cellular leakage and hepatic protein release(Şahin et al, \u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e2024\u003c/span\u003e), through the Fenton reaction, wherein Fe\u0026sup2;⁺ reacts with hydrogen peroxide (H₂O₂) to produce hydroxyl radicals (\u0026bull;OH) one of the most damaging ROS (ang \u003cem\u003eet al\u003c/em\u003e, 2025). Selenium in this present study, did not only normalized the hepatic enzymes activities but also affected total protein (TP) levels, to potentially facilitate timely restoration of hepatocyte function and reduced protein catabolism as well as acute hepatic cytolysis. Selenium\u0026rsquo;s role in ameliorating oxidative liver injury (Goltyaev and Varlamova, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec29\" class=\"Section2\"\u003e\u003ch2\u003e4.4. Renal activities\u003c/h2\u003e\u003cp\u003eTable\u0026nbsp;2 show serum creatinine, urea, and uric acid were significantly elevated by Fe-NTA, to mediate impaired glomerular filtration and renal oxidative damage. Selenium administration show a reversed activities of these indices inconsistent with prior studies (Achuba and colleague, 2018) affirming selenium\u0026rsquo;s renoprotective efficacy (Sharma \u003cem\u003eet al\u003c/em\u003e., 2017). Partial correction of electrolyte imbalances, particularly for sodium and bicarbonate level. This further gives credence on selenium involvement to improve renal tubular functions in line with (Trigueira et al, \u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Notably, increased potassium levels in selenium-treated groups reflect electron complex interactions in renal ion transport under antioxidant activities and modulation (Hussein \u003cem\u003eet al\u003c/em\u003e,2022). Selenium action is primarily exerted through incorporation into selenoproteins to activate glutathione peroxidases (GPx) and thioredoxin reductases (Chaudi\u0026egrave;re, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). These enzymes maintain cellular redox balance by reduction of ROS generation from hydrogen peroxide (H₂O₂) and lipid hydroperoxides, thereby preventing excessive oxidative stress linked to aging and diseases such as cancer, cardiovascular disease, and neurodegeneration (Engwa et al, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec30\" class=\"Section2\"\u003e\u003ch2\u003e4.5. Histomorphology\u003c/h2\u003e\u003cp\u003eIn our study, rats exposed to Fe-NTA alone exhibited classic signs of acute hepatocellular injury, including coagulative necrosis(3a-B) notably in the centrilobular zone with preservation of tissue architecture but widespread loss of hepatocyte cords, atrophy, and cytoplasmic degeneration. These conditions are true reflectance of both direct oxidative damage and metabolic failure in zone 3 hepatocytes, and reduced antioxidant capacity compared to periportal (zone 1) hepatocytes (Panday et al, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). The coagulative necrosis observed is consistent with oxidative collapse of the cytoskeleton and membrane integrity, where cellular proteins are denatured, yet tissue outlines remain preserved, hallmark of ischemic or toxic hepatic injury (Schuermans et al, \u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Additionally, hepatocyte atrophy and degeneration in this region further support the level of sustained oxidative insult, leading to impaired protein synthesis, mitochondrial swelling, and cell shrinkage (Anastasopoulos et al, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2023\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eDietary supplementation with selenium, a trace element with potent antioxidant function (Acuba and colleague 2018), demonstrated dose-dependent hepatoprotection (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003ea A-E). Selenium is incorporated into several selenoproteins, most notably glutathione enzymes and thioredoxin reductases, which directly detoxify hydrogen peroxide and lipid hydroperoxides (Chaudi\u0026egrave;re, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), thus limiting the propagation of free radicals and subsequent membrane lipid damage (Recknagel, et al, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). At a supplementation level of 0.6 mg Se, show in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003ea-C, partial hepatoprotection was observed. Histological sections revealed moderate improvement, with a reduction in the extent of necrosis and preservation of some hepatocyte cords. However, residual cellular degeneration and cytoplasmic vacuolization indicated that the antioxidant defense was incompletely restored at this dose. Increasing the selenium supplementation to 0.8 mg produced a more pronounced protective effect (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003ea-C). The liver histology showed marked attenuation of necrosis, with improved hepatocyte morphology, reconstitution of lobular architecture, and fewer degenerative changes in the centrilobular region(Choi, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). This suggests that at this dose, selenium may have enhanced glutathione expression or activity to a level sufficient to counteract the Fe-NTA-induced oxidative burden.\u003c/p\u003e\u003cp\u003eThe most significant histological protection was observed in the group fed with 1.0 mg Se where liver architecture appeared near-normal, with minimal evidence of centrilobular necrosis or hepatocyte atrophy (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003ea-E). Preservation of hepatocyte cords, absence of cytoplasmic degeneration, and restoration of nuclear integrity strongly support the maximal antioxidant and possibly anti-inflammatory effect at this dosage(Mohammed and Al-Shawi, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). In addition to upregulating antioxidant enzymes, higher selenium doses may also inhibit NF-κB-mediated inflammatory responses and promote Nrf2 (nuclear factor erythroid 2\u0026ndash;related factor 2) activation, enhancing cellular resilience to oxidative injury (Altanam et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2025\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eKidney histology in the Fe-NTA alone group revealed profound architectural distortion, with accentuation of renal cortical and medullary structures, indicating reactive changes secondary to injury. Mesangial cell proliferation was evident within the glomeruli, reflecting an inflammatory and fibrogenic response likely mediated by oxidative stress-induced cytokines, such as TGF-β and IL-6 related factors promoting extracellular matrix expansion (Efiong, et al, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). The observed ectasia (dilation) of tubular lumens suggests loss of tubular epithelial integrity and compensatory dilation following epithelial cell injury or apoptosis. These findings aligned with previous report of Schelling, (\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Tubular atrophy, evidenced by thinning of tubular epithelium and loss of brush border, further indicates chronic oxidative damage and impaired regenerative capacity, these features were also reported in previous study of Cortinovis et al, (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe introduction of selenium supplementation resulted in a marked amelioration of Fe-NTA-induced renal pathology. At a dose of 0.6 mg Se, partial histological improvement was observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003eb-C). While accentuation and mesangial proliferation were still present, the degree of tubular ectasia and atrophy was notably reduced, and patches of normal renal cells were identifiable. This suggests that at lower dose of selenium was sufficient to partially restore redox homeostasis but may not have fully suppressed the inflammatory and fibrotic signaling pathways activated by Fe-NTA. With 0.8 mg Se, the kidneys (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003eb-D) exhibited improved architecture, with significant reduction in glomerular hypercellularity, attenuation of mesangial expansion, and restoration of normal tubular morphology in large regions. Only minimal ectasia and atrophy were present, and normal renal histological conditions predominated. This indicates an enhanced antioxidant response and potential modulation of transcriptional regulators such as Nrf2, which governs cellular antioxidant (Altanam et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). In the 1.0 mg Se group, the renal histology was essentially indistinguishable from normal controls (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003eb-E). There was no evidence of mesangial proliferation, ectasia, or tubular atrophy, and the kidneys showed well-preserved glomerular and tubular structures, with abundant normal renal epithelial cells. This further suggests that at this dosage, selenium effectively neutralized Fe-NTA induced oxidative stress, likely by maximizing the activity of GPx and other selenoproteins(Chaudi\u0026egrave;re, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), thereby halting lipid peroxidation and secondary inflammatory responses (Altanam et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). In addition, selenium may also suppress pro-apoptotic pathways, prserving the mitochondrial integrity and supporting cell survival (Murray et al, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2018\u003c/span\u003e)\u003c/p\u003e\u003c/div\u003e"},{"header":"5.0. Conclusion","content":"\u003cp\u003eThe study posit selenium (Se) supplementation to confers significant protective effects against ferric nitrilotriacetate (Fe-NTA) induced hepato-, and nephrotoxicity in rats, primarily through modulation of oxidative stress, and inflammatory response crucial for immune modulation, and organ histological indices, although, the study sorely support previous established activities of selenium as a potent antioxidant and anti-inflammatory agent, but novelly deviated in the milieu of metal-induced toxicity and for the first time recognized it\u0026rsquo;s ameliorative potentials on Fe-NTA toxicity.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eConflict of Interest:\u003c/h2\u003e\u003cp\u003eNone declared.\u003c/p\u003e\u003ch2\u003eEthics Approval:\u003c/h2\u003e\u003cp\u003e Study protocol was done in consonance with the guide lines and declarations of Animal Research Ethics (2009) and the World Medical Association (2016) on animal use in bio-medical research and it conformed to the animal rights law in an approval granted by the Faculty of Science ethical committee of Delta State University, Abraka with reference number REL/FOS/2023/11\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eNo external funding was received for this study, all funds were provided by the authors\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eA CONCEPTUALIZATION OF RESEARCHA.B. WROTE THE MAIN MANUSCRIPT.C.D. DATA ANALYSIS AND PREPARATION OF FIGUREE GENERAL SUPERVISION.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eMr. Andy Ohwokevwo for supporting the research during laboratory analysis\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAchuba, F. I., \u0026amp; Obaremi, C. (2018). Effects of selenium fortified diet on inflammatory markers in Wistar albino rats exposed to crude oil. \u003cem\u003eNigerian Journal of Pharmaceutical and Biomedical Research\u003c/em\u003e, \u003cem\u003e3\u003c/em\u003e(3), 209\u0026ndash;216.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAdewale, G. G., Olajide, P. A., Omowumi, O. S., Okunlola, D. D., Taiwo, A. M., \u0026amp; Adetuyi, B. O. (2022). Toxicological Significance of the Occurrence of Selenium in Foods. \u003cem\u003eWorld News of Natural Sciences (WNOFNS)\u003c/em\u003e, \u003cem\u003e44\u003c/em\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAhmed, A. R., Vun-Sang, S., \u0026amp; Iqbal, M. (2022). Therapeutic role of nitroglycerin against copper-nitrilotriacetate induced hepatic and renal damage. \u003cem\u003eHuman \u0026amp; Experimental Toxicology\u003c/em\u003e, \u003cem\u003e41\u003c/em\u003e, 09603271221131312.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAkramipour, R., Golpayegani, M. R., Ghasemi, M., Noori, N., \u0026amp; Fattahi, N. (2019). Development of an efficient sample preparation method for the speciation of Se (iv)/Se (vi) and total inorganic selenium in blood of children with acute leukemia. \u003cem\u003eNew Journal of Chemistry\u003c/em\u003e, \u003cem\u003e43\u003c/em\u003e(18), 6951\u0026ndash;6958.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAl Knani, Z. M. I., Al Ashoor, A. S., \u0026amp; Hussein, A. N. Assessment of antioxidant activity in Vaucheria sessilis extracts and their efficacy against isolated Candida spp. from diabetic foot ulcers.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAltanam, S. Y., Darwish, N., \u0026amp; Bakillah, A. (2025). Exploring the Interplay of Antioxidants, Inflammation, and Oxidative Stress: Mechanisms, Therapeutic Potential, and Clinical Implications. \u003cem\u003eDiseases\u003c/em\u003e, \u003cem\u003e13\u003c/em\u003e(9), 309.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAnastasopoulos, N. A., Charchanti, A. V., Barbouti, A., Mastoridou, E. M., Goussia, A. C., Karampa, A. D., \u0026amp; Glantzounis, G. K. (2023). The role of oxidative stress and cellular senescence in the pathogenesis of metabolic associated fatty liver disease and related hepatocellular carcinoma. \u003cem\u003eAntioxidants\u003c/em\u003e, \u003cem\u003e12\u003c/em\u003e(6), 1269.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAnwar, F., Al-Abbasi, F. A., Bhatt, P. C., Ahmad, A., Sethi, N., \u0026amp; Kumar, V. (2015). Umbelliferone β-d-galactopyranoside inhibits chemically induced renal carcinogenesis via alteration of oxidative stress, hyperproliferation and inflammation: possible role of NF-κB. \u003cem\u003eToxicology Research\u003c/em\u003e, \u003cem\u003e4\u003c/em\u003e(5), 1308\u0026ndash;1323.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAwai, M., Narasaki, M., Yamanoi, Y., \u0026amp; Seno, S. (1979). Induction of diabetes in animals by parenteral administration of ferric nitrilotriacetate. A model of experimental hemochromatosis. \u003cem\u003eThe American Journal of Pathology\u003c/em\u003e, \u003cem\u003e95\u003c/em\u003e(3), 663.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBarchielli, G., Capperucci, A., \u0026amp; Tanini, D. (2022). The role of selenium in pathologies: an updated review. \u003cem\u003eAntioxidants\u003c/em\u003e, \u003cem\u003e11\u003c/em\u003e(2), 251..\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBartels, H., Bohmer, M., \u0026amp; Heierli, C. J. C. C. A. (1972). Estimation of serum creatinine without removal of protein.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBen-Azu, B., Uruaka, C. I., Ajayi, A. M., Jarikre, T. A., Nwangwa, K. E., Chilaka, K. C., \u0026hellip; Agu, G. O. (2023). Reversal and preventive pleiotropic mechanisms involved in the antipsychotic-like effect of taurine, an essential β-amino acid in ketamine-induced experimental schizophrenia in mice. \u003cem\u003eNeurochemical research\u003c/em\u003e, \u003cem\u003e48\u003c/em\u003e(3), 816\u0026ndash;829.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eB\u0026uuml;ttner, P., Obradovic, D., Wunderlich, S., Feistritzer, H. J., Holzwirth, E., Lauten, P., \u0026hellip; Thiele, H. (2020). Selenoprotein P in myocardial infarction with cardiogenic shock. \u003cem\u003eShock\u003c/em\u003e, \u003cem\u003e53\u003c/em\u003e(1), 58\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCARAWAY, W. T., \u0026amp; HALD, P. M. (1963). Uric acid. In \u003cem\u003eStandard methods of clinical chemistry\u003c/em\u003e (Vol. 4, pp. 239\u0026ndash;247). Elsevier.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChaudi\u0026egrave;re, J. (2023). Biological and catalytic properties of selenoproteins. \u003cem\u003eInternational Journal of Molecular Sciences\u003c/em\u003e, \u003cem\u003e24\u003c/em\u003e(12), 10109.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChoi, J. H. (2025). Histological and Molecular Evaluation of Liver Biopsies: A Practical and Updated Review. \u003cem\u003eInternational Journal of Molecular Sciences\u003c/em\u003e, \u003cem\u003e26\u003c/em\u003e(16), 7729.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCortinovis, M., Perico, N., \u0026amp; Remuzzi, G. (2024). Tubulointerstitial injury in proteinuric chronic kidney diseases. \u003cem\u003eFrontiers in Medicine\u003c/em\u003e, \u003cem\u003e11\u003c/em\u003e, 1478697.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCrocker J, Burnett D (2005) \u0026lsquo;CGH array analysis of human tissues\u0026rsquo;. The science of laboratory diagnosis, eds 2nd edn. Wiley, pp 523\u0026ndash;8\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDonia, T., Dabbour, N. M., \u0026amp; Loutfy, S. A. (2023). Hesperidin: advances on resources, biosynthesis pathway, bioavailability, bioactivity, and pharmacology. In \u003cem\u003eHandbook of dietary flavonoids\u003c/em\u003e (pp. 1\u0026ndash;55). Cham: Springer International Publishing.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEddie-Amadi, B. F., Vangone, R., Guerretti, V., Ozoani, H. A., Okolo, K. O., Awolayeofori, D., \u0026hellip; Guerriero, G. (2025). Ovary Metal Toxicity Remediation by Agro-Food Waste: Evidence for a Regulatory Mechanism of Oxidative Stress by Banana (Musa cavendish) Peel Extract. \u003cem\u003eAntioxidants\u003c/em\u003e, \u003cem\u003e14\u003c/em\u003e(9), 1129.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEfiong, E. E., Maedler, K., Effa, E., Osuagwu, U. L., Peters, E., Ikebiuro, J. O., \u0026hellip; Grallert, H. (2025). Decoding diabetic kidney disease: a comprehensive review of interconnected pathways, molecular mediators, and therapeutic insights. \u003cem\u003eDiabetology \u0026amp; Metabolic Syndrome\u003c/em\u003e, \u003cem\u003e17\u003c/em\u003e(1), 192.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEkayoda, O., Kadiri, H. E., \u0026amp; Ohwokevwo, O. A. (2022). Combined effects of cadmium-and cyanide-contaminated diet on oxidative stress biomarkers in different tissues of rats. \u003cem\u003eGalician Med. J\u003c/em\u003e, \u003cem\u003e29\u003c/em\u003e(4), E202244.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEl-Demerdash, F. M., Minjal, A. H., El-Sayed, R. A., \u0026amp; Baghdadi, H. H. (2024). Hepatoprotective effect of ethanolic pomegranate peel extract against levofloxacin via suppression of oxidative stress, proinflammation, and apoptosis in male rats. \u003cem\u003eJournal of Medicinal Food\u003c/em\u003e, \u003cem\u003e27\u003c/em\u003e(9), 866\u0026ndash;878.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEllman GL (1959). Determination of sulfhydryl group. Arch. Biochem. Biophys., 82: 70\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEngwa, G. A., Nweke, F. N., \u0026amp; Nkeh-Chungag, B. N. (2022). Free radicals, oxidative stress-related diseases and antioxidant supplementation. \u003cem\u003eAlternative Therapies in Health \u0026amp; Medicine\u003c/em\u003e, \u003cem\u003e28\u003c/em\u003e(1).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGado, F., Ferrario, G., Della Vedova, L., Zoanni, B., Altomare, A., Carini, M., \u0026hellip; Baron, G. (2023). Targeting Nrf2 and NF-κB signaling pathways in cancer prevention: The role of apple phytochemicals. \u003cem\u003eMolecules\u003c/em\u003e, \u003cem\u003e28\u003c/em\u003e(3), 1356.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGoltyaev, M. V., \u0026amp; Varlamova, E. G. (2023). The role of selenium nanoparticles in the treatment of liver pathologies of various natures. \u003cem\u003eInternational journal of molecular sciences\u003c/em\u003e, \u003cem\u003e24\u003c/em\u003e(13), 10547.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGrellner, W., Georg, T., \u0026amp; Wilske, J. (2000). Quantitative analysis of proinflammatory cytokines (IL-1β, IL-6, TNF-α) in human skin wounds. \u003cem\u003eForensic science international\u003c/em\u003e, \u003cem\u003e113\u003c/em\u003e(1\u0026ndash;3), 251\u0026ndash;264.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHuang, G., Zang, J., He, L., Zhu, H., Huang, J., Yuan, Z., \u0026amp; Xu, A. (2021). Bioactive nanoenzyme reverses oxidative damage and endoplasmic reticulum stress in neurons under ischemic stroke. \u003cem\u003eACS nano\u003c/em\u003e, \u003cem\u003e16\u003c/em\u003e(1), 431\u0026ndash;452.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHuang, H., Qiu, Y., Tang, A., Li, W., Yao, W., Zhong, M., \u0026hellip; Zou, T. (2023). The impact of food restriction on liver enzyme levels: a systematic review and meta-analysis. \u003cem\u003eNutrition Reviews\u003c/em\u003e, \u003cem\u003e81\u003c/em\u003e(8), 939\u0026ndash;950.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHussein, J., Farouk, H., \u0026amp; El-Khayat, Z. (2022). Therapeutic Efficacy of Selenium in Management of Hyperhomocytenemia in Cisplatin-Induced Nephrotoxicity. \u003cem\u003eBiomedical and Pharmacology Journal\u003c/em\u003e, \u003cem\u003e15\u003c/em\u003e(4), 1905\u0026ndash;1915.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIchipi-Ifukor, P. C., Asagba, S. O., Kweki, G. R., \u0026amp; Nwose, C. (2019). Attenuation of oxidative enzymes induction in palm oil fractions pre-treated cadmium intoxicated rats.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIchipi-Ifukor, P. C., Asagba, S. O., Nwose, C., Mordi, J. C., \u0026amp; Oyem, J. C. (2022). Palm oil extracts protected against cadmium chloride poisoning via inhibition of oxidative stress in rats. \u003cem\u003eBulletin of the National Research Centre\u003c/em\u003e, \u003cem\u003e46\u003c/em\u003e(1), 5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIqbal, M., Shah, M. D., Vun-Sang, S., Okazaki, Y., \u0026amp; Okada, S. (2021). The therapeutic potential of curcumin in alleviating N-diethylnitrosamine and iron nitrilotriacetate induced renal cell tumours in mice via inhibition of oxidative stress: Implications for cancer chemoprevention. \u003cem\u003eBiomedicine \u0026amp; Pharmacotherapy\u003c/em\u003e, \u003cem\u003e139\u003c/em\u003e, 111636.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIwetan, B. B., Kweki, G. R., Onobrudu, D. A., Ugochukwu, U., Andy, O. O., Ewhre, L. O., \u0026amp; Obianime, A. W. (2025). Hepatorenal protection of Justicia carnea leaf aqueous extract on sheep red blood cell-induced immunotoxicity in mice. \u003cem\u003eTropical Journal of Pharmaceutical Research\u003c/em\u003e, \u003cem\u003e24\u003c/em\u003e(5).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIwetan, B. B., Obianime, A. W., Ewhre, L. O., \u0026amp; Kweki, G. R. (2022). The Antioxidant Modulating Properties of Justicia carnea Extract on Sheep Red Blood Cells Immunized Mice. \u003cem\u003eJ. Pharmaceut. Res. Int\u003c/em\u003e, \u003cem\u003e34\u003c/em\u003e(33B), 58\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJomova, K., Alomar, S. Y., Valko, R., Nepovimova, E., Kuca, K., \u0026amp; Valko, M. (2025). The role of redox-active iron, copper, manganese, and redox-inactive zinc in toxicity, oxidative stress, and human diseases. \u003cem\u003eEXCLI journal\u003c/em\u003e, \u003cem\u003e24\u003c/em\u003e, 880.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKieliszek, M. (2023). Selenium in the prevention of SARS-CoV-2 and other viruses. \u003cem\u003eBiological Trace Element Research\u003c/em\u003e, \u003cem\u003e201\u003c/em\u003e(2), 655\u0026ndash;662.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKipp, A. P., Strohm, D., Brigelius-Floh\u0026eacute;, R., Schomburg, L., Bechthold, A. E., Leschik-Bonnet, E., \u0026amp; German Nutrition Society (DGE. (2015). Revised reference values for selenium intake. \u003cem\u003eJournal of trace elements in medicine and biology\u003c/em\u003e, \u003cem\u003e32\u003c/em\u003e, 195\u0026ndash;199.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKweki, G. R., Ichipi-Ifukor, P. C., \u0026amp; Asagba, S. O. (2018). High caffeine-containing energy drink-induced metabolic stress in rats. \u003cem\u003eSokoto Journal of Medical Laboratory Science\u003c/em\u003e, \u003cem\u003e3\u003c/em\u003e(3).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLeibold, E., Deckardt, K., Mellert, W., Potthoff-Karl, B., Grundler, O., \u0026amp; J\u0026auml;ckh, R. (2002). NTA and Fe (III) NTA: differential patterns of renal toxicity in subchronic studies. \u003cem\u003eHuman \u0026amp; Experimental Toxicology\u003c/em\u003e, \u003cem\u003e21\u003c/em\u003e(8), 445\u0026ndash;452.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMaruna, R. F. L. (1957). Estimation of serum sodium: a critical study of colorimetric methods of estimation and description of a simple photometric method\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMisra, H. P., \u0026amp; Fridovich, I. (1978). Inhibition of superoxide dismutases by azide. \u003cem\u003eArchives of biochemistry and biophysics\u003c/em\u003e, \u003cem\u003e189\u003c/em\u003e(2), 317\u0026ndash;322.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMohammed, R. A., \u0026amp; Al-Shawi, N. N. (2025). Butein mitigates 5-FU-triggered hepatotoxicity via antioxidant, anti-inflammatory, and anti-apoptotic pathways. \u003cem\u003eToxicology Reports\u003c/em\u003e, 102120.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMurray, D., Mirzayans, R., \u0026amp; McBride, W. H. (2018). Defenses against pro-oxidant forces-Maintenance of cellular and genomic integrity and longevity. \u003cem\u003eRadiation research\u003c/em\u003e, \u003cem\u003e190\u003c/em\u003e(4), 331\u0026ndash;349.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOkada, K., Fukui, M., \u0026amp; Zhu, B. T. (2016). Protein disulfide isomerase mediates glutathione depletion-induced cytotoxicity. \u003cem\u003eBiochemical and biophysical research communications\u003c/em\u003e, \u003cem\u003e477\u003c/em\u003e(3), 495\u0026ndash;502.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOkazaki, Y. (2022). The role of ferric nitrilotriacetate in renal carcinogenesis and cell death: from animal models to clinical implications. \u003cem\u003eCancers\u003c/em\u003e, \u003cem\u003e14\u003c/em\u003e(6), 1495.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOlarotimi, O. J. (2020). Serum electrolyte balance and antioxidant status of broiler chickens fed diets containing varied levels of monosodium glutamate (MSG). \u003cem\u003eBulletin of the National Research Centre\u003c/em\u003e, \u003cem\u003e44\u003c/em\u003e, 1\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOlayanju, J. B., Bozic, D., Naidoo, U., \u0026amp; Sadik, O. A. (2024). A comparative review of key isothiocyanates and their health benefits. \u003cem\u003eNutrients\u003c/em\u003e, \u003cem\u003e16\u003c/em\u003e(6), 757.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOlivera, J. (2020). \u003cem\u003eRoles of ZIP14 in Iron Overload-Related Endocrinopathies\u003c/em\u003e (Doctoral dissertation, University of Florida).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOzoani, H. A., Ezejiofor, A. N., Orish, C. N., Dokubo, A., Offor, S. J., Uwah, A. F., \u0026hellip; Orisakwe, O. E. (2025). Hepatorenal protection of food supplement (Prosopis africana) in rat following metal mixture exposure via alternations in oxido-inflammatory markers. \u003cem\u003eDiscover Food\u003c/em\u003e, \u003cem\u003e5\u003c/em\u003e(1), 154.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOzoani, H., Ezejiofor, A. N., Okolo, K. O., Orish, C. N., Cirovic, A., Cirovic, A., \u0026amp; Orisakwe, O. E. (2023). Zinc and selenium attenuate quaternary heavy metal mixture-induced testicular damage via amplification of the antioxidant system, reduction in metal accumulation, inflammatory and apoptotic biomarkers. \u003cem\u003eToxicological Research\u003c/em\u003e, \u003cem\u003e39\u003c/em\u003e(3), 497\u0026ndash;515.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePanday, R., Monckton, C. P., \u0026amp; Khetani, S. R. (2022, February). The role of liver zonation in physiology, regeneration, and disease. In \u003cem\u003eSeminars in liver disease\u003c/em\u003e (Vol. 42, No. 01, pp. 001\u0026ndash;016). Thieme Medical Publishers, Inc\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRadwan, R. R. (2012). \u003cem\u003ePharmacological Study of the Effect of Certain Natural Products on Doxorubicin-induced Nephropathy in Rats Exposed to Low Doses of Radiation\u003c/em\u003e (No. INIS-EG\u0026ndash;391). Faculty of Pharmacy, Cairo University, Cairo (Egypt).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRahbardar, M. G., Farmad, H. C., Hosseinzadeh, H., \u0026amp; Mehri, S. (2021). Protective effects of selenium on acrylamide-induced neurotoxicity and hepatotoxicity in rats. \u003cem\u003eIranian Journal of Basic Medical Sciences\u003c/em\u003e, \u003cem\u003e24\u003c/em\u003e(8), 1041.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRamesh, R. K., \u0026amp; Suresh, V. (2022). Biomolecules and Pharmacology of Tabernaemontana divaricata (L.) R. Br. ex Roem. \u0026amp; Schult. \u003cem\u003eBioactives and Pharmacology of Medicinal Plants\u003c/em\u003e, 121\u0026ndash;137.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRecknagel, R. O., Glende, E. A., \u0026amp; Britton, R. S. (2020). Free radical damage and lipid peroxidation. In \u003cem\u003eHepatotoxicology\u003c/em\u003e (pp. 401\u0026ndash;436). CRC press.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eReitman, S., \u0026amp; Frankel, S. (1957). A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. \u003cem\u003eAmerican journal of clinical pathology\u003c/em\u003e, \u003cem\u003e28\u003c/em\u003e(1), 56\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRenu, K., Gopalakrishnan, A. V., \u0026amp; Madhyastha, H. (2025). Is periodontitis triggering an inflammatory response in the liver, and does this reaction entail oxidative stress?. \u003cem\u003eOdontology\u003c/em\u003e, \u003cem\u003e113\u003c/em\u003e(3), 889\u0026ndash;902.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRick, W., Fritsch, W. P., \u0026amp; Szasz, G. (1972). Fortschritte der klinischen Enzymologie. \u003cem\u003eDMW-Deutsche Medizinische Wochenschrift\u003c/em\u003e, \u003cem\u003e97\u003c/em\u003e(47), 1828\u0026ndash;1834.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eŞAHIN, I. K., SEZER, C. V., \u0026amp; AYHANCI, A. (2024). THE EFFECTS OF OXIDATIVE STRESS ON CELLULAR STRUCTURES: LIPID PEROXIDATION. \u003cem\u003eOXIDATIVE STRESS AND ANTIOXIDANT DEFENSE SYSTEMS\u003c/em\u003e, 15.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSahoo, D. K., Heilmann, R. M., Paital, B., Patel, A., Yadav, V. K., Wong, D., \u0026amp; Jergens, A. E. (2023). Oxidative stress, hormones, and effects of natural antioxidants on intestinal inflammation in inflammatory bowel disease. \u003cem\u003eFrontiers in endocrinology\u003c/em\u003e, \u003cem\u003e14\u003c/em\u003e, 1217165.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSaito, Y. (2022). Essential trace element selenium and redox regulation: its metabolism, physiological function, and related diseases. \u003cem\u003eRedox Experimental Medicine\u003c/em\u003e, \u003cem\u003e2022\u003c/em\u003e(1), R149-R158.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchelling, J. R. (2016). Tubular atrophy in the pathogenesis of chronic kidney disease progression. \u003cem\u003ePediatric nephrology\u003c/em\u003e, \u003cem\u003e31\u003c/em\u003e(5), 693\u0026ndash;706.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchuermans, S., Kestens, C., \u0026amp; Marques, P. E. (2024). Systemic mechanisms of necrotic cell debris clearance. \u003cem\u003eCell Death \u0026amp; Disease\u003c/em\u003e, \u003cem\u003e15\u003c/em\u003e(8), 557.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShahbaz, M., Naeem, H., Imran, M., Ul Hassan, H., Alsagaby, S. A., Al Abdulmonem, W., \u0026hellip; Ihsan, A. (2023). Chrysin a promising anticancer agent: recent perspectives. \u003cem\u003eInternational Journal of Food Properties\u003c/em\u003e, \u003cem\u003e26\u003c/em\u003e(1), 2294\u0026ndash;2337.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShimada, B. K., Takayama, N. A., Hallam, K. A., Pjd, S., Yew, J. Y., Alfulaij, N., \u0026hellip; Seale, L. A. (2025). A selenomethionine deficient, high-fructose diet does not lead to cardiometabolic disorder in the selenocysteine lyase knockout mice. \u003cem\u003eJournal of Trace Elements in Medicine and Biology\u003c/em\u003e, \u003cem\u003e90\u003c/em\u003e, 127685.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSkeggs Jr, L. T., \u0026amp; Hochstrasser, H. (1964). Multiple automatic sequential analysis. \u003cem\u003eClinical Chemistry\u003c/em\u003e, \u003cem\u003e10\u003c/em\u003e(10), 918\u0026ndash;936.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTietz, S., Puthiyaveetil, S., Enlow, H. M., Yarbrough, R., Wood, M., Semchonok, D. A., \u0026hellip; Kirchhoff, H. (2015). Functional implications of photosystem II crystal formation in photosynthetic membranes. \u003cem\u003eJournal of Biological Chemistry\u003c/em\u003e, \u003cem\u003e290\u003c/em\u003e(22), 14091\u0026ndash;14106.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTilak, J. C., \u0026amp; Devasagayam, T. P. (2006). Oxidative damage to mitochondria. In \u003cem\u003eOxidative Stress, Disease and Cancer\u003c/em\u003e (pp. 85\u0026ndash;150).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eToyokuni, S., Kong, Y., Cheng, Z., Sato, K., Hayashi, S., Ito, F. and Akatsuka, S. (2020). Carcinogenesis as side effects of iron and oxygen utilization: from the unveiled truth toward ultimate bioengineering. \u003cem\u003eCancers\u003c/em\u003e, \u003cem\u003e12\u003c/em\u003e(11), 3320.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTrigueira, P. D. C., Leal, V. D. O., Cardoso, B. R., Mafra, D., Araujo, M. C., \u0026amp; Stockler-Pinto, M. B. (2024). Selenium supplementation in chronic kidney disease patients undergoing haemodialysis: a systematic review of the effects on plasma selenium, antioxidant and inflammatory markers, immunological parameters and thyroid hormones. \u003cem\u003eNutrition research reviews\u003c/em\u003e, 1\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTrinder, P. (1951). A rapid method for the determination of sodium in serum. \u003cem\u003eAnalyst\u003c/em\u003e, \u003cem\u003e76\u003c/em\u003e(907), 596\u0026ndash;599.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eU. Rehman, M., \u0026amp; Sultana, S. (2011). Attenuation of oxidative stress, inflammation and early markers of tumor promotion by caffeic acid in Fe-NTA exposed kidneys of Wistar rats. \u003cem\u003eMolecular and cellular biochemistry\u003c/em\u003e, \u003cem\u003e357\u003c/em\u003e(1), 115\u0026ndash;124.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eValko, M. M. H. C. M., Morris, H., \u0026amp; Cronin, M. T. D. (2005). Metals, toxicity and oxidative stress. \u003cem\u003eCurrent medicinal chemistry\u003c/em\u003e, \u003cem\u003e12\u003c/em\u003e(10), 1161\u0026ndash;1208.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang, D., Zhou, J., Sun, X., \u0026amp; Niu, X. (2025). The Essence of Nature Can be the Simplest (3) Holistic Energy: Extracellular Fenton Reactions of All Cells. \u003cem\u003eChemistry \u0026amp; Biodiversity\u003c/em\u003e, \u003cem\u003e22\u003c/em\u003e(7), e202500942.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWatkins, J. M., Clark, N. M., Song, G., Oliveira, C. C., Mishra, B., Brachova, L., \u0026hellip; Jones, A. M. (2021). Phosphorylation dynamics in a flg22-induced, heterotrimeric G-protein dependent signaling network in Arabidopsis thaliana reveals a candidate PP2A phosphatase involved in AtRGS1 trafficking. \u003cem\u003eBioRxiv\u003c/em\u003e, 2021-12.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWeatherburn, M. (1967). Phenol-hypochlorite reaction for determination of ammonia. \u003cem\u003eAnalytical chemistry\u003c/em\u003e, \u003cem\u003e39\u003c/em\u003e(8), 971\u0026ndash;974.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang, R., Liu, Y., Xing, L., Zhao, N., Zheng, Q., Li, J., \u0026amp; Bao, J. (2018). The protective role of selenium against cadmium-induced hepatotoxicity in laying hens: expression of Hsps and inflammation-related genes and modulation of elements homeostasis. \u003cem\u003eEcotoxicology and environmental safety\u003c/em\u003e, \u003cem\u003e159\u003c/em\u003e, 205\u0026ndash;212.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhao, J., Zhang, X., Li, Y., Yu, J., Chen, Z., Niu, Y., \u0026hellip; Wu, J. (2023). Interorgan communication with the liver: novel mechanisms and therapeutic targets. \u003cem\u003eFrontiers in immunology\u003c/em\u003e, \u003cem\u003e14\u003c/em\u003e, 1314123.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhou, Z., Wu, H., Yang, R., Xu, A., Zhang, Q., Dong, J. \u0026amp; Sun, M. (2020). GSH depletion liposome adjuvant for augmenting the photothermal immunotherapy of breast cancer. \u003cem\u003eScience advances\u003c/em\u003e, \u003cem\u003e6\u003c/em\u003e(36), eabc4373.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Ferric Nitrilotriacetate, Selenium, Selenoproteins, glutathione, Superoxide dismutase, pro-inflammatory cytokines, nephrotoxicity, hepatoxicity","lastPublishedDoi":"10.21203/rs.3.rs-7909439/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7909439/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eFerric nitrilotriacetate (Fe-NTA) is a nephrotoxic compound known to induce acute renal injury through oxidative stress mediated by the Fenton reaction. This study investigated the ameliorating potential of selenium supplementation against Fe-NTA-induced toxicity. Fifty male Wistar albino rats were divided into five groups and acclimatized for two weeks. Except group I and II that served as normal control and negative control, all animals received intraperitoneal injection (\u003cem\u003ei.p\u003c/em\u003e) of Fe-NTA (3.0 mg/kg) every other day for 14 days. From day 15 to 28, groups III, IV, and V were fed diets supplemented with sodium selenite at doses of 0.06, 0.08, and 0.1 mg, while group II rats were exposed to 3 mg/kg (\u003cem\u003ei.p\u003c/em\u003e) of Fe-NTA respectively. On day 29, biochemical and histological analyses of blood and tissue samples was conducted. Fe-NTA administration resulted in significant oxidative stress, indicated by elevated malondialdehyde (MDA) levels and decreased antioxidant markers (GSH, SOD, CAT, GST), alongside increased pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and notable hepatic and renal damage. However, Selenium supplementation significantly reversed these effects, improving antioxidant enzymes activities and reducing inflammation along histopathological alterations. These findings from the study show the dietary impact of selenium intake to protect hepatic and renal tissues against Fe-NTA-mediated oxidative and inflammatory toxicity in Wistar rats\u003c/p\u003e","manuscriptTitle":"Selenium Intake Modulates Hepato and Nephrotoxic Responses in Rats Exposed to Ferric Nitrilotriacetate (Fe-NTA)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-24 10:39:19","doi":"10.21203/rs.3.rs-7909439/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9932a6b0-52f6-4b45-9c8d-d3d506d7c5f0","owner":[],"postedDate":"November 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-22T12:53:45+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-24 10:39:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7909439","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7909439","identity":"rs-7909439","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}