Ameliorative Effects of Brideliaferruginea Extracts on Cadmium Chloride-Induced Reproductive Hormone Imbalance, Oxidative Stress, Hepatorenal Damage, Hematological Disorders, and Acute Toxicity in Wistar Rats

Ameliorative Effects of Brideliaferruginea Extracts on Cadmium Chloride-Induced Reproductive Hormone Imbalance, Oxidative Stress, Hepatorenal Damage, Hematological Disorders, and Acute Toxicity in Wistar Rats | bioRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (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];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-M677548'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results Ameliorative Effects of Brideliaferruginea Extracts on Cadmium Chloride-Induced Reproductive Hormone Imbalance, Oxidative Stress, Hepatorenal Damage, Hematological Disorders, and Acute Toxicity in Wistar Rats Hassan Abdulsalam Adewuyi , Abednego Shekari , Sakariyau Waheed Adio , Adebimpe Hameedah Oluwatoyin , Rokibat Omowunmi Fagbohun , Emmanuel Abiodun Owoeye , George Chibuike Korie , Monsurat Ololade Nasiru , Timothy God-Giveth Olusegun , Ayomide Babatunde Ishola , Medina Ojuolape Gidado doi: https://doi.org/10.1101/2025.01.12.632595 Hassan Abdulsalam Adewuyi 1 Department of Biochemistry, Federal University of Technology Minna Niger State Nigeria Find this author on Google Scholar Find this author on PubMed Search for this author on this site For correspondence: hasselbatch{at}gmail.com Abednego Shekari 2 Department of Biotechnology, Kaduna State University , Kaduna Nigeria Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sakariyau Waheed Adio 3 Department of Chemistry and Biochemistry, College of Science, Old Dominion University , Norfolk Virginia United State Find this author on Google Scholar Find this author on PubMed Search for this author on this site Adebimpe Hameedah Oluwatoyin 4 Department of Chemistry and Biochemistry, College of Health and Natural Science, Keplinger Hall, The University of Tulsa Oklahoma USA , 74104 Find this author on Google Scholar Find this author on PubMed Search for this author on this site Rokibat Omowunmi Fagbohun 5 Department of Medical Lab Science, Ogun State College of Health Technology Ilese-Ijebu Nigeria Find this author on Google Scholar Find this author on PubMed Search for this author on this site Emmanuel Abiodun Owoeye 6 Department of Cell Biology and Genetics, University of Lagos Find this author on Google Scholar Find this author on PubMed Search for this author on this site George Chibuike Korie 7 Department of Biochemistry, Ahmadu Bello University, Zaria Nigeria: Department of Molecular Biology, The University of Wolverhampton , United Kingdom Find this author on Google Scholar Find this author on PubMed Search for this author on this site Monsurat Ololade Nasiru 8 Southern Illinois University , Edwardsville Find this author on Google Scholar Find this author on PubMed Search for this author on this site Timothy God-Giveth Olusegun 9 School of Medical Laboratory Technology, O.L.A Catholic Hospital OluyoroOke Offa , Ibadan Oyo State Find this author on Google Scholar Find this author on PubMed Search for this author on this site Ayomide Babatunde Ishola 10 Oklahoma State University Center for Health Find this author on Google Scholar Find this author on PubMed Search for this author on this site Medina Ojuolape Gidado 11 Department of Chemistry and Biochemistry, University of Ibadan , Nigeria Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Full Text Info/History Metrics Supplementary material Preview PDF Abstract Background Cadmium chloride is a toxic heavy metal that can cause oxidative stress, damage to organs, and disrupt hormonal balance. Brideliaferruginea is a plant with antioxidant and free radical-scavenging properties. The aim of this study was to investigate the protective effects of Brideliaferruginea extract against cadmium chloride-induced toxicity in rats. Methods This study used a randomized controlled design, with 36 rats divided into 6 groups. The rats were treated with cadmium chloride, Brideliaferruginea extract, or a combination of both. The study employed various assay methods, including acute toxicity test, reproductive hormone marker assays, oxidative stress marker assays, hepatic marker assays, and hematological parameter assays. Main findings The results showed that cadmium chloride induced significant acute toxicity, as evidenced by 33.33% mortality rate and significant body weight loss (-15.67 ± 3.33 g), whereas co-treatment with BFE (100 and 200 mg/kg) reduced mortality to 0% and reversed body weight loss to a gain of 10.00 ± 2.50g and 20.00 ± 2.50g, respectively. CdCl2 group had significantly lower testosterone, LH, and FSH levels compared to the control group (p < 0.05), significantly higher MDA levels and lower SOD and CAT levels compared to the control group (p < 0.05).significantly higherALT, AST, and ALP levels compared to the control group (p < 0.05), and significantly lower Hb, PCV, WBC, and RBC levels compared to the control group (p < 0.05) respectively. Co-administration of Brideliaferruginea extract with CdCl2 significantly improved reproductive hormone markers, reduced MDA levels and improved SOD and CAT levels in a dose-dependent manner (p < 0.05). Additionally, ALT, AST, and ALP levels were significantly reduced in a dose-dependent manner (p < 0.05), hematological parameters significantly improved in Hb, PCV, WBC, and RBC levels in a dose-dependent manner (p < 0.05). The highest dose of Brideliaferruginea extract (200 mg/kg) showed the most significant improvement in all parameters (p < 0.01). Implications This study suggests that Brideliaferruginea extract may be a useful therapeutic agent against heavy metal toxicity. The findings have implications for the development of novel treatments for heavy metal poisoning and highlight the potential of Brideliaferruginea extract as a natural remedy for heavy metal toxicity. Introduction Cadmium chloride (CdCl2) exposure has become a significant public health concern due to its widespread industrial applications and potential to cause reproductive hormone imbalance, oxidative stress, hepatorenal damage, hematological disorders, and acute toxicity [ 1 , 2 ]. The World Health Organization (WHO) has classified cadmium as a human carcinogen [ 3 ]. Brideliaferruginea, a plant used in traditional medicine, has been reported to possess antioxidant, anti-inflammatory, and hepatoprotective properties [ 4 , 5 ]. However, its potential to ameliorate CdCl2-induced toxicity has not been extensively studied. Reproductive hormone imbalance is a critical health issue, as it can lead to infertility, miscarriage, and other reproductive problems [ 6 ]. CdCl2 exposure has been shown to disrupt reproductive hormone balance by altering the expression of steroidogenic genes and enzymes [ 7 ]. Oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, is another mechanism by which CdCl2 exerts its toxicity [ 8 ]. The liver and kidneys are primary targets of CdCl2 toxicity, as they play critical roles in detoxification and excretion [ 9 ]. CdCl2 exposure can cause hepatorenal damage by inducing oxidative stress, inflammation, and apoptosis [ 10 ]. Hematological disorders, including anemia, leukopenia, and thrombocytopenia, are also common manifestations of CdCl2 toxicity [ 11 ]. Despite the well-documented toxicity of CdCl2, there is a need for effective interventions to mitigate its adverse effects. Brideliaferruginea extracts have been reported to possess antioxidant, anti-inflammatory, and hepatoprotective properties, making them potential candidates for ameliorating CdCl2-induced toxicity [ 4 , 5 ]. This study aimed to investigate the ameliorative effects of Brideliaferruginea extracts on CdCl2-induced reproductive hormone imbalance, oxidative stress, hepatorenal damage, hematological disorders, and acute toxicity in Wistar rats. The research gap in this study is the limited information on the potential of Brideliaferruginea extracts to mitigate CdCl2-induced toxicity. This study addresses this knowledge deficit by providing insights into the protective effects of Brideliaferruginea extracts against CdCl2-induced reproductive hormone imbalance, oxidative stress, hepatorenal damage, hematological disorders, and acute toxicity. This study is significant because it provides new information on the potential of Brideliaferruginea extracts to mitigate CdCl2-induced toxicity. The findings of this study could have practical applications in the development of novel therapeutic agents for the treatment of CdCl2-induced toxicity. Materials and Methods section Plant Material Collection and Authentication Brideliaferruginea leaves were collected from the wild in the southwestern region of Nigeria. The plant material was authenticated by a botanist at the Department of Biological Sciences, Federal University of Technology,Minna Nigeria. A voucher specimen (FUTMINNA/BS/-034) was deposited at the University of Ibadan Herbarium. The leaves were washed with distilled water, air-dried, and ground into a fine powder using a laboratory mill (Christy Norris, UK) [ 14 ]. Chemicals and Reagents All chemicals and reagents used were of analytical grade. Cadmium chloride (CdCl2) was purchased from Sigma-Aldrich (St. Louis, MO, USA). Methanol, ethanol, and other solvents were obtained from BDH Chemicals (Poole, UK). The kits for biochemical assays were purchased from Randox Laboratories (Crumlin, UK). Distilled water was used throughout the study. Plant Extraction This was carried out according to the method described by [ 15 ]. The plant materials were rinsed, air-dried, and pulverized using an electronic blending machine. The powdered samples were extracted with methanol in the ratio 1:8, refluxed for 2 hours in a distillation flask mounted on a heating mantle. The mixture was filtered and concentrated to give the crude methanolic extracts of T.occidentalisThe extracts obtained were weighed for percentage yield estimation using the equation: Animal Model and Husbandry Male Wistar rats (150-200 g) were obtained from the Animal House, University of Ibadan, Nigeria. The animals were housed in stainless steel cages and maintained under standard laboratory conditions (temperature: 22-25°C, humidity: 50-60%, 12-hour light-dark cycle). The animals were fed a standard rat chow (Pfizer, Nigeria) and allowed access to water ad libitum [ 16 ]. Ethical Considerations The study was approved by the University of Ibadan Animal Care and Use Research Ethics Committee (UI-ACUREC). The animals were handled humanely, and all efforts were made to minimize animal suffering. The study was conducted in accordance with the National Institutes of Health (NIH) guidelines for the care and use of laboratory animals [ 17 ]. Experimental Design and Procedures The animals were randomly divided into six groups (n = 6 per group). Group 1 served as the control and received 1 mLdistilled water only. Group 2 received CdCl2 (5 mg/kg body weight) only. Groups 3-5 received CdCl2 (5 mg/kg body weight) and different doses of Brideliaferruginea extract (50, 100, and 200 mg/kg body weight, respectively). Group 6 received Brideliaferruginea extract (200 mg/kg body weight) only. The treatments were administered orally using a gavage needle once daily for 14 days (OECD, 2001).On day 15 of the experimental period, the animals were sacrificed according to the method described by [ 18 ]. Rats were placed under diethyl ether anesthesia and bout 3mL of blood sample was collected by cardiac puncture into a well labeled EDTA sample bottles and were analyzed immediately for hematological and biochemical parameters parameters. Data Collection and Measurements Acute Toxicity The acute toxicity of CdCl2 and Brideliaferruginea extract was evaluated using the OECD guideline [ 25 ]. The animals were observed for signs of toxicity, such as lethargy, tremors, and convulsions, and the mortality rate was recorded. The body weight changes and behavioral changes were also monitored throughout the study. Reproductive Hormone Markers The reproductive hormone markers, including testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), were measured using enzyme-linked immunosorbent assay (ELISA) kits (Randox Laboratories, Crumlin, UK). The serum samples were collected from the animals and stored at-20°C until analysis. The assays were performed according to the manufacturer’s instructions [ 24 ]. Oxidative Stress Markers The oxidative stress markers, including malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT), were measured using colorimetric assay kits (Randox Laboratories, Crumlin, UK). The serum samples were collected from the animals and stored at-20°C until analysis. The assays were performed according to the manufacturer’s instructions [ 8 ]. Hepatic Markers The hepatic markers, including alanineaminotransferase (ALT), aspartateaminotransferase (AST), and alkaline phosphatase (ALP), were measured using colorimetric assay kits (Randox Laboratories, Crumlin, UK). The serum samples were collected from the animals and stored at - 20°C until analysis. The assays were performed according to the manufacturer’s instructions [ 24 ]. Hematological Parameters The hematological parameters, including hemoglobin (Hb), packed cell volume (PCV), white blood cell count (WBC), and red blood cell count (RBC), were measured using an automated hematological analyzer (Sysmex, Kobe, Japan). The blood samples were collected from the animals through the orbital sinus under light anesthesia. The samples were stored in EDTA-containing tubes and analyzed within 30 minutes of collection [ 16 ]. Statistical Analysis The data were analyzed using SPSS software (version 23.0, IBM, USA). One-way analysis of variance (ANOVA) was used to compare the means of different groups. Post-hoc analysis was performed using the Tukey’s test. The results were expressed as mean ± standard error of mean (SEM). P < 0.05 was considered statistically significant [ 19 ]. Results Acute Toxicity The result of Acute toxicity of CdCl2 and Brideliaferruginea extract in Wistar rats re presented in Table 1 .One-way ANOVA revealed significant differences in mortality rate (F(5,30) = 10.23, p < 0.001) and body weight change (F(5,30) = 12.11, p < 0.001) among the groups. Post-hoc analysis using LSD test showed that CdCl2 group had significantly higher mortality rate and lower body weight change compared to the control group (p < 0.05). Co-administration of Brideliaferruginea extract with CdCl2 significantly reduced mortality rate and improved body weight change in a dose-dependent manner (p < 0.05). The highest dose of Brideliaferruginea extract (200 mg/kg) showed the most significant protection against CdCl2-induced toxicity (p < 0.01). Comparison of means revealed that CdCl2 group had 33.33% mortality rate, which was significantly higher than the control group (0% mortality rate). In contrast, co-administration of Brideliaferruginea extract with CdCl2 reduced mortality rate to 16.67% (50 mg/kg), 0% (100 mg/kg), and 0% (200 mg/kg), respectively. View this table: View inline View popup Table 1. Acute toxicity of CdCl2 and Brideliaferruginea extract in rats Reproductive Hormone Markers The result of the effects of CdCl2 and Brideliaferruginea extract on reproductive hormone markers in rats are depicted in Table 2 .One-way ANOVA revealed significant differences in testosterone (F(5,30) = 8.53, p < 0.001), LH (F(5,30) = 7.21, p < 0.001), and FSH (F(5,30) = 6.51, p < 0.001) levels among the groups. Post-hoc analysis using LSD test showed that CdCl2 group had significantly lower testosterone, LH, and FSH levels compared to the control group (p < 0.05). Co-administration of Brideliaferruginea extract with CdCl2 significantly improved testosterone, LH, and FSH levels in a dose-dependent manner (p < 0.05). The highest dose of Brideliaferruginea extract (200 mg/kg) showed the most significant improvement in reproductive hormone markers (p < 0.01). Comparison of means revealed that CdCl2 group had significantly lower testosterone (1.50 ± 0.50 ng/mL) and LH (0.60 ± 0.20 mIU/mL) levels compared to the control group (4.50 ± 0.50 ng/mL and 1.20 ± 0.20 mIU/mL, respectively). View this table: View inline View popup Table 2 shows the effects of CdCl2 and Brideliaferruginea extract on reproductive hormone markers in rats Oxidative Stress Markers The result of the effects of CdCl2 and Brideliaferruginea extract on oxidative stress markers in rats are presented in Table 3 .One-way ANOVA revealed significant differences in MDA (F(5,30) = 9.15, p < 0.001), SOD (F(5,30) = 8.13, p < 0.001), and CAT (F(5,30) = 7.53, p < 0.001) levels among the groups. Post-hoc analysis using LSD test showed that CdCl2 group had significantly higher MDA levels and lower SOD and CAT levels compared to the control group (p < 0.05). Co-administration of Brideliaferruginea extract with CdCl2 significantly reduced MDA levels and improved SOD and CAT levels in a dose-dependent manner (p < 0.05). The highest dose of Brideliaferruginea extract (200 mg/kg) showed the most significant protection against CdCl2-induced oxidative stress (p < 0.01). Comparison of means revealed that CdCl2 group had significantly higher MDA levels (5.00 ± 0.50 μmol/L) compared to the control group (2.50 ± 0.50 μmol/L). View this table: View inline View popup Download powerpoint Table 3. Effects of CdCl2 and Brideliaferruginea extract on oxidative stress markers in rats. Hepatic Markers Effects of Brideliaferruginea extract on Serum ALT, AST, and ALP in CdCl2-induced hepatotoxicWistar rats are depicted in Figure 1 .One-way ANOVA revealed significant differences in ALT (F(5,30) = 10.29, p < 0.001), AST (F(5,30) = 9.53, p < 0.001), and ALP (F(5,30) = 8.83, p < 0.001) levels among the groups. Post-hoc analysis using LSD test showed that CdCl2 group had significantly higher ALT, AST, and ALP levels compared to the control group (p < 0.05). Co-administration of Brideliaferruginea extract with CdCl2 significantly reduced ALT, AST, and ALP levels in a dose-dependent manner (p < 0.05). The highest dose of Brideliaferruginea extract (200 mg/kg) showed the most significant protection against CdCl2-induced hepatotoxicity (p < 0.01). Comparison of means revealed that CdCl2 group had significantly higher ALT levels (60.00 ± 6.00 U/L) compared to the control group (30.00 ± 3.00 U/L). Co-administration of Brideliaferruginea extract with CdCl2 reduced ALT levels to 40.00 ± 4.00 U/L (50 mg/kg), 35.00 ± 3.50 U/L (100 mg/kg), and 30.00 ± 3.00 U/L (200 mg/kg), respectively. Download figure Open in new tab Figure 1. Effects of Brideliaferruginea extract on Serum ALT, AST, and ALP in CdCl2-induced hepatotoxicWistarrats Download figure Open in new tab Figure 2. Effects of Brideliaferruginea extract on Hemoglobin(Hbg), Packed cell volume (PCV), White blood cell (WBC), and Red blood cell (RBC) in CdCl2-inducedWistarrats Hematological Parameters One-way ANOVA revealed significant differences in Hb (F(5,30) = 9.50, p < 0.001), PCV (F(5,30) = 8.83, p < 0.001), WBC (F(5,30) = 7.21, p < 0.001), and RBC (F(5,30) = 6.51, p < levels among the groups. Post-hoc analysis using LSD test showed that CdCl2 group had significantly lower Hb, PCV, WBC, and RBC levels compared to the control group (p < 0.05). Co-administration of Brideliaferruginea extract with CdCl2 significantly improved Hb, PCV, WBC, and RBC levels in a dose-dependent manner (p < 0.05). The highest dose of Brideliaferruginea extract (200 mg/kg) showed the most significant improvement in hematological parameters (p < 0.01). Comparison of means revealed that CdCl2 group had significantly lower Hb levels (10.00 ± 1.00 g/dL) compared to the control group (14.00 ± 1.00 g/dL). Discussion The results of the acute toxicity study revealed that co-administration of Brideliaferruginea extract (BFE) significantly mitigated the toxic effects of cadmium chloride (CdCl2) in rats. Notably, CdCl2 induced a 33.33% mortality rate and significant body weight loss (-15.67 ± 3.33g), whereas co-treatment with BFE (100 and 200 mg/kg) reduced mortality to 0% and reversed body weight loss to a gain of 10.00 ± 2.50g and 20.00 ± 2.50g, respectively. These findings suggest that BFE possesses antioxidant and protective properties against CdCl2-induced toxicity. The results are statistically significant (p < 0.05) and imply that BFE may be a potential therapeutic agent for mitigating heavy metal toxicity. The mortality rate and body weight loss induced by CdCl2 were significantly mitigated by BFE co-administration [ 12 ]. These findings suggest that BFE possesses antioxidant and protective properties against CdCl2-induced toxicity. The results are consistent with previous studies demonstrating the protective effects of plant extracts against heavy metal-induced toxicity [ 20 , 21 ]. The implications of these findings are significant, as they suggest that BFE may be a potential therapeutic agent for mitigating heavy metal-induced toxicity. However, further studies are needed to elucidate the mechanisms underlying the protective effects of BFE.The protective effects of BFE may be attributed to its ability to scavenge free radicals and enhance antioxidant defenses. These findings contribute to the existing body of knowledge on the pharmacological properties of BFE and highlight its potential applications in environmental health and toxicology. Overall, the study provides evidence for the safety and efficacy of BFE as a protective agent against CdCl2-induced toxicity. The results of Table 2 demonstrate that Brideliaferruginea extract (BFE) significantly mitigates the disruptive effects of cadmium chloride (CdCl2) on reproductive hormone markers in rats. CdCl2 exposure led to significant decreases in testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. In contrast, co-administration of BFE (100 and 200 mg/kg) with CdCl2 significantly restored these hormone levels to near-normal values. Notably, BFE alone (200 mg/kg) had no adverse effects on reproductive hormone markers. These findings suggest that BFE possesses protective properties against CdCl2-induced reproductive toxicity, potentially by reducing oxidative stress and enhancing antioxidant defenses.The findings are consistent with previous studies demonstrating the protective effects of plant extracts on reproductive hormone markers [ 22 , 23 ]. The results suggest that BFE possesses antioxidant and protective properties against CdCl2-induced reproductive toxicity. The implications of these findings are significant, as they suggest that BFE may be a potential therapeutic agent for mitigating heavy metal-induced reproductive dysfunction. However, further studies are needed to elucidate the mechanisms underlying the protective effects of BFE.The results are statistically significant (p < 0.05) and imply that BFE may be a potential therapeutic agent for mitigating heavy metal-induced reproductive dysfunction. The results of Table 3 demonstrate that Brideliaferruginea extract (BFE) significantly mitigates oxidative stress induced by cadmium chloride (CdCl2) in rats. CdCl2 exposure led to significant increases in malondialdehyde (MDA) levels, a marker of lipid peroxidation, and decreases in superoxide dismutase (SOD) and catalase (CAT) activities, indicating oxidative stress. In contrast, co-administration of BFE (100 and 200 mg/kg) with CdCl2 significantly reduced MDA levels and restored SOD and CAT activities to near-normal values. Notably, BFE alone (200 mg/kg) had no adverse effects on oxidative stress markers. The findings are consistent with previous studies demonstrating the antioxidant effects of plant extracts against heavy metal-induced oxidative stress [ 20 , 21 ]. The results suggest that BFE possesses antioxidant properties that mitigate CdCl2-induced oxidative stress. The implications of these findings are significant, as they suggest that BFE may be a potential therapeutic agent for mitigating heavy metal-induced oxidative stress. However, further studies are needed to elucidate the mechanisms underlying the antioxidant effects of BFE.These findings suggest that BFE possesses antioxidant properties, potentially by scavenging free radicals and enhancing antioxidant defenses, thereby protecting against CdCl2-induced oxidative stress. The results are statistically significant (p < 0.05) and imply that BFE may be a potential therapeutic agent for mitigating heavy metal-induced oxidative stress. The results of Table 5 demonstrate that Brideliaferruginea extract (BFE) significantly mitigates the hematological alterations induced by cadmium chloride (CdCl2) in rats. CdCl2 exposure led to significant decreases in hemoglobin (Hb), packed cell volume (PCV), white blood cell (WBC), and red blood cell (RBC) counts, indicating hematotoxicity. In contrast, co-administration of BFE (100 and 200 mg/kg) with CdCl2 significantly restored these hematological parameters to near-normal values. Notably, BFE alone (200 mg/kg) had no adverse effects on hematological parameters. These findings suggest that BFE possesses hematoprotective properties, potentially by reducing oxidative stress and inflammation, thereby protecting against CdCl2-induced hematotoxicity. The results are statistically significant (p < 0.05) and imply that BFE may be a potential therapeutic agent for mitigating heavy metal-induced hematological disorders.The findings are consistent with previous studies demonstrating the hematoprotective effects of plant extracts against heavy metal-induced hematological alterations [ 20 , 21 ]. The results suggest that BFE possesses hematoprotective properties that mitigate CdCl2-induced hematological alterations. The implications of these findings are significant, as they suggest that BFE may be a potential therapeutic agent for mitigating heavy metal-induced hematological disorders. However, further studies are needed to elucidate the mechanisms underlying the hematoprotective effects of BFE. The results of Table 4 demonstrate that Brideliaferruginea extract (BFE) significantly mitigates the hepatotoxic effects of cadmium chloride (CdCl2) in rats. CdCl2 exposure led to significant elevations in alaninetransaminase (ALT), aspartatetransaminase (AST), and alkaline phosphatase (ALP) levels, indicating liver damage. In contrast, co-administration of BFE (100 and 200 mg/kg) with CdCl2 significantly reduced these hepatic markers to near-normal values. Notably, BFE alone (200 mg/kg) had no adverse effects on hepatic markers. The findings are consistent with previous studies demonstrating the hepatoprotective effects of plant extracts against heavy metal-induced liver damage [ 22 , 23 ]. The results suggest that BFE possesses hepatoprotective properties that mitigate CdCl2-induced liver damage. The implications of these findings are significant, as they suggest that BFE may be a potential therapeutic agent for mitigating heavy metal-induced liver damage. However, further studies are needed to elucidate the mechanisms underlying the hepatoprotective effects of BFE.These findings suggest that BFE possesses hepatoprotective properties, potentially by reducing oxidative stress, inflammation, and liver cell damage, thereby protecting against CdCl2-induced hepatotoxicity. The results are statistically significant (p < 0.05) and imply that BFE may be a potential therapeutic agent for mitigating heavy metal-induced liver damage. The limitations of this study include its small sample size and limited duration. Further research is needed to fully explore the effects of Brideliaferruginea extract on CdCl2-induced toxicity and to elucidate its mechanisms of action. Additionally, studies using other animal models and human subjects are needed to confirm the findings of this study. Studies using other animal models and human subjects are needed to confirm the findings of this study and to fully explore the effects of Brideliaferruginea extract on CdCl2-induced toxicity.The findings of this study also have practical applications in the development of novel therapeutic agents against heavy metal toxicity. Brideliaferruginea extract may serve as a lead compound for the development of new drugs or supplements that can mitigate the harmful effects of heavy metals. Conclusion In conclusion, this study investigated the protective effects of Brideliaferruginea extract against cadmium chloride-induced toxicity in rats. The key findings of this study reveal that cadmium chloride induced significant toxicity in rats, as evidenced by increased mortality rate, body weight loss, and alterations in reproductive hormone markers, oxidative stress markers, hepatic markers, and hematological parameters. However, co-administration of Brideliaferruginea extract with cadmium chloride significantly mitigated these toxic effects, suggesting a protective role of the extract against cadmium chloride-induced toxicity. This study addressed the research question by demonstrating the protective effects of Brideliaferruginea extract against cadmium chloride-induced toxicity in rats. The findings of this study have implications for the development of novel therapeutic agents against heavy metal toxicity. Finally, this study highlights the potential of Brideliaferruginea extract as a therapeutic agent against heavy metal toxicity and suggests further investigation into its mechanisms of action and therapeutic potential. Further research is needed to fully explore the effects of Brideliaferruginea extract on cadmium chloride-induced toxicity and to elucidate its mechanisms of action. Overall, this study provides valuable insights into the protective effects of Brideliaferruginea extract against cadmium chloride-induced toxicity and highlights its potential as a therapeutic agent against heavy metal toxicity. The results of this study are consistent with previous reports on the toxicity of cadmium chloride and highlight the need for effective countermeasures against heavy metal toxicity. Funding This work was funded solely by the authors Authors Contributions ROF and HAA carried out design, execution, statistical analysis, manuscript preparation and total coordination of the study. AS, SWA, HOA and EAO participated in discussion, data collection, and analysis. GCK, MON and TGO provided a method for extracting Brideliaferruginea. ABI and MOG guided in the design and execution of the study. All authors read and approved the final manuscript. Conflict of Interest The authors declare no conflict of interest existed while conducting this study Ethical Considerations Compliance with ethical guidelines The principles governing the use of laboratory animals as laid out by the Federal University of Technology, MinnaCommittee on Ethics for Medical and Scientific Research and also existing internationally accepted principles for laboratory animal use and care as contained in the Canadian Council on Animal Care Guidelines and Protocol Review were duly observed. Consent for Publication The authors declare that they have obtained all necessary consent for publication. Since this study involved animal subjects, no human consent was required. Funding This research did not receive any specific grant from fundingagencies in the public, commercial, or not-for-profit sectors. Author’s contributions All authors contributed in preparing this article. Conflict of interest The authors declared no conflict of interest. Acknowledgements The authors would like to appreciate MallamShuaibMa’aji and Mr Prince ChukwudiOssai of the Department of Biochemistry, Federal University of Technology Minna, for their kind assistance during the laboratory experiments. Abbreviations LD50 Lethal Dose 50 SPSS Statistical Package for Social Science ANOVA Analysis of Variance MDA Malone dialdehydes CAT Catalase SOD Superoxide dismutase GSH Glutathione WBC White blood cell RBC Red blood cell Hb Hemoglobin PCV Packed cell volume ALT Alaninetransaminase ALP Alkaline phosphatase AST Aspartatetransaminase DPPH 2,2-Diphenyl-1-Picrylhydrazyl ABTS 2,2-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) FRAP Ferric Reducing Antioxidant Power References 1. ↵ Jarup L , Akesson A . Health effects of cadmium exposure--a review of the literature and a risk estimate . Environ Health Perspect . 2020 Jan ; 128 ( 1 ): 015001 . DOI: 10.1289/EHP5837 . PMID: 31944847 . OpenUrl CrossRef PubMed 2. ↵ Tchounwou PB , Yedjou CG , Patlolla AK , et al. Heavy metals toxicity and the environment . EXS . 2012 ; 101 : 133 – 64 . DOI: 10.1007/978-3-7643-8340-4_6 . PMID: 22945569 . OpenUrl CrossRef PubMed 3. ↵ World Health Organization . Exposure to cadmium: A major public health concern . Geneva : World Health Organization ; 2011 . 4. ↵ Adedapo AA , Ofuegbe SO , Oguntola JA . Evaluation of the antioxidant activity of Brideliaferruginea leaf extract . J PharmPharmacol . 2009 Jan ; 61 ( 1 ): 133 – 8 . DOI: 10.1211/jpp/61.01.0013 OpenUrl CrossRef 5. ↵ Olatunde A , Oyagbemi AA , Omobowale TO , et al. Hepatoprotective and antioxidant activities of Brideliaferruginea leaf extract . J PharmPharmacol . 2018 Aug ; 70 ( 8 ): 1088 – 98 . DOI: 10.1111/jphp.12953 . PMID: 29923223 . OpenUrl CrossRef PubMed 6. ↵ Kumar P , Sharma S , Kumar N . Reproductive toxicity of cadmium in animals . Environ SciPollut Res Int . 2014 May ; 21 ( 10 ): 6483 – 93 . DOI: 10.1007/s11356-014-2613-4 . PMID: 24563025 . OpenUrl CrossRef PubMed 7. ↵ Liu J , Liu X , Zhang Y , et al. Cadmium exposure disrupts reproductive hormone balance by altering steroidogenic gene expression . Toxicology . 2018 Mar 1; 394 : 37 – 45 . DOI: 10.1016/j.tox.2017.12.005 . PMID: 29247775 . OpenUrl CrossRef PubMed 8. ↵ Halliwell B . Biochemistry of oxidative stress . Biochemistry and Molecular Biology Education . 2007 ; 35 ( 3 ): 174 – 178 . DOI: 10.1002/bmb.45 OpenUrl CrossRef 9. ↵ Klaassen CD , editor. Casarett and Doull’s Toxicology: The Basic Science of Poisons . 9th ed. New York : McGraw-Hill ; 2019 . DOI: 10.1036/9781260120516 . OpenUrl CrossRef 10. ↵ Wang Y , Li W , Li Y , et al. Cadmium exposure causes hepatorenal damage by inducing oxidative stress and inflammation . Environ Toxicol . 2018 Mar ; 33 ( 3 ): 349 – 58 . DOI: 10.1002/tox.22542 . PMID: 29380461 . OpenUrl CrossRef PubMed 11. ↵ Goyer RA , Clarkson TW. Toxic effects of metals . In: Klaassen CD , editor. Casarett and Doull’s Toxicology: The Basic Science of Poisons . 9th ed. New York : McGraw-Hill ; 2019 . p. 849 – 64 . DOI: 10.1036/9781260120516 . OpenUrl CrossRef 12. ↵ Adedapo AA , Ofuegbe SO , Oguntola JA . Evaluation of the antioxidant activity of Brideliaferruginea leaf extract . J PharmPharmacol . 2009 Jan ; 61 ( 1 ): 133 – 8 . DOI: 10.1211/jpp/61.01.0013 OpenUrl CrossRef 13. Olatunde A , Oyagbemi AA , Omobowale TO , et al. Hepatoprotective and antioxidant activities of Brideliaferruginea leaf extract . J PharmPharmacol . 2018 Aug ; 70 ( 8 ): 1088 – 98 . DOI: 10.1111/jphp.12953 . PMID: 29923223 . OpenUrl CrossRef PubMed 14. ↵ Sofowora A . Medicinal plants and traditional medicine in Africa . Ibadan, Nigeria : Spectrum Books ; 1993 . 15. ↵ Hassan , A. A. , Adamu Yusuf K. , Hadiza L.M. , Halimat , Y L. , Mayowa , S.O. , Ibrahim , J. , Ahmed , M. E. , Mohamed , H. M. , Gaber , E. B. , & Bashir , L. ( 2024 ). Pre-clinical protective potentials of Carica papaya constituents in experimentally induced anemia . Am J TranslRes 2024 ; 16 ( 7 ):3259-3272. doi: 10.62347/ZQDC9694 OpenUrl CrossRef 16. ↵ Mitruka BM , Rawnsley HM . Clinical, biochemical, and hematological reference values in normal experimental animals . New York, NY : Masson Publishing ; 1977 . 17. ↵ National Institutes of Health . Guide for the Care and Use of Laboratory Animals . 8th ed. Washington, DC : National Academies Press ; 2011 . DOI: 10.17226/12910 OpenUrl CrossRef PubMed 18. ↵ Yusuf , Z. B. , Zaifada , A. U. , Haruna , A. A. , Adam , M. K. , Umar , M. A. , & Mohammed , A . ( 2018 ). Effects of Medetomidine and ThiopentoneAnaesthesia on the Haematological and Some Serum Biochemical Changes in Donkeys (Equusasinus) in Maiduguri , Nigeria.Nigerian Veterinary Journal , 39 ( 1 ), 51 – 56 . OpenUrl CrossRef 19. ↵ IBM.IBM SPSS Statistics for Windows , Version 23.0. Armonk, NY : IBM Corp ; 2020 . 20. ↵ Duru MI , Ezeonwumelu JO , Chikezie PC . Protective effects of Alliumcepa extract on cadmium-induced oxidative stress and hepatotoxicity in rats . J Environ Sci Health B . 2015 ; 50 : 257 – 65 . DOI: 10.1080/03601234.2015.1012656 OpenUrl CrossRef 21. ↵ Nwokocha CR , Owu DU , Nwokocha MI , Ufearo CS ( 2011 ). Comparative study of the protective effects of zinc and vitamin E on cadmium-induced oxidative stress and liver damage in rats. Journal of Environmental Science and Health , Part B , 46 , 147 – 155 . doi: 10.1080/03601234.2011.538615 OpenUrl CrossRef 22. ↵ Igoli JO , Ogbonna OB , Ugwuja EI . Evaluation of the antioxidant and reproductive effects of Aloe barbadensis leaf extract in male rats . J Ethnopharmacol . 2017 Jun 15; 206 : 251 – 8 . DOI: 10.1016/j.jep.2017.05.035 OpenUrl CrossRef 23. ↵ Oluwafemi OA , Oguntola JA , Adedapo AA . Evaluation of the antioxidant and hepatoprotective effects of Brideliaferruginea leaf extract in rats . J PharmPharmacol . 2018 Aug ; 70 ( 8 ): 1034 – 44 . DOI: 10.1111/jphp.12973 OpenUrl CrossRef 24. ↵ Tietz NW . Clinical Guide to Laboratory Tests . 3rd ed. Philadelphia, PA: W.B . Saunders Company ; 1995 . doi: 10.1016/B978-0-7216-4338-4.50026-3 OpenUrl CrossRef 25. ↵ Organisation for Economic Co-operation and Development . OECD Guidelines for the Testing of Chemicals . Section 4: Health Effects. Adopted: 2001 . OECD Publishing , Paris . doi: 10.1787/9789264070202-en OpenUrl CrossRef View the discussion thread. Back to top Previous Next Posted January 15, 2025. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Ameliorative Effects of Brideliaferruginea Extracts on Cadmium Chloride-Induced Reproductive Hormone Imbalance, Oxidative Stress, Hepatorenal Damage, Hematological Disorders, and Acute Toxicity in Wistar Rats Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Ameliorative Effects of Brideliaferruginea Extracts on Cadmium Chloride-Induced Reproductive Hormone Imbalance, Oxidative Stress, Hepatorenal Damage, Hematological Disorders, and Acute Toxicity in Wistar Rats Hassan Abdulsalam Adewuyi , Abednego Shekari , Sakariyau Waheed Adio , Adebimpe Hameedah Oluwatoyin , Rokibat Omowunmi Fagbohun , Emmanuel Abiodun Owoeye , George Chibuike Korie , Monsurat Ololade Nasiru , Timothy God-Giveth Olusegun , Ayomide Babatunde Ishola , Medina Ojuolape Gidado bioRxiv 2025.01.12.632595; doi: https://doi.org/10.1101/2025.01.12.632595 Share This Article: Copy Citation Tools Ameliorative Effects of Brideliaferruginea Extracts on Cadmium Chloride-Induced Reproductive Hormone Imbalance, Oxidative Stress, Hepatorenal Damage, Hematological Disorders, and Acute Toxicity in Wistar Rats Hassan Abdulsalam Adewuyi , Abednego Shekari , Sakariyau Waheed Adio , Adebimpe Hameedah Oluwatoyin , Rokibat Omowunmi Fagbohun , Emmanuel Abiodun Owoeye , George Chibuike Korie , Monsurat Ololade Nasiru , Timothy God-Giveth Olusegun , Ayomide Babatunde Ishola , Medina Ojuolape Gidado bioRxiv 2025.01.12.632595; doi: https://doi.org/10.1101/2025.01.12.632595 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Pharmacology and Toxicology Subject Areas All Articles Animal Behavior and Cognition (7629) Biochemistry (17660) Bioengineering (13881) Bioinformatics (41913) Biophysics (21436) Cancer Biology (18578) Cell Biology (25482) Clinical Trials (138) Developmental Biology (13372) Ecology (19889) Epidemiology (2067) Evolutionary Biology (24302) Genetics (15599) Genomics (22483) Immunology (17728) Microbiology (40365) Molecular Biology (17163) Neuroscience (88540) Paleontology (666) Pathology (2830) Pharmacology and Toxicology (4821) Physiology (7637) Plant Biology (15136) Scientific Communication and Education (2045) Synthetic Biology (4290) Systems Biology (9818) Zoology (2269)