Cardioprotective Potentials of Vernonia amygdalina on 1,2-Dimethylhydrazine Induced Toxicity in Rats

Cardioprotective Potentials of Vernonia amygdalina on 1,2-Dimethylhydrazine Induced Toxicity in Rats | 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 Cardioprotective Potentials of Vernonia amygdalina on 1,2-Dimethylhydrazine Induced Toxicity in Rats Augustine Osasemeaga Okpiabhele, Osahon Daniel Abu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8029156/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 Background Cardiotoxicity is an emerging condition that occurs due to systemic toxicity resulting from 1,2 dimethylhydrazine (DMH) exposure. Until now, nothing is known about the role of Vernonia amygdalina in suppressing lipid abnormalities and oxidative stress caused by DMH cardiotoxicity in rats. Our novel treatment measures tend to be beneficial in combating heart toxicity resulting from DMH exposure. This study was conducted to investigate the cardioprotective potentials of Vernonia amygdalina on 1,2-Dimethylhydrazine induced toxicity in rats . Methods Adult male Wistar rats were exposed to 1, 2 dimethylhydrazine (DMH) toxicity via the intraperitoneal route at a single dose of 40 mg/kg body weight before and after treatment with lower (200 mg/kg body weight) and higher (400 mg/kg body weight) doses of Vernonia amygdalina ethanol extract. Lipid profile parameters, cardiovascular disease risks factors and oxidative stress markers were measured in plasma and heart tissue homogenates of rats using standardized protocols, while portions of the excised heart specimens were subjected to histopathological examination. Data analysis and post-hoc test for this study were performed using SPSS version 20. Results The concentrations of heart tissue antioxidant enzymes (CAT, SOD, GPx, GSH, GR and GSH (%)) in the DMH group were significantly reduced (p<0.05) relative to control and the other groups. However, administration of ethanol extract of V. amygdalina to rats significantly increased (p<0.05) these levels when compared with the DMH group. Furthermore, there was a significant decrease (p<0.05) in the mean values of cardiovascular disease risk factors, cardiac Nitric Oxide (NO), and Malondialdehyde (MDA) in the treatment groups when compared with control and DMH group. Heart tissues of DMH-induced rats treated with Vernonia amygdalina revealed a significant reduction (p<0.05) in organ weight relative to the control group. Histological studies revealed the protective and regenerative effects of Vernonia amygdalina on heart tissues. Conclusions The findings from this study indicates that Vernonia amygdalina can effectively suppress irregularities in the lipid profile, cardiovascular disease risk factors, and oxidative stress parameters caused by DMH toxicity due to its antioxidant properties. This impliesthat Vernonia amygdalina holds promise as a novel therapeutic strategy for improving DMH systemic toxicity. Toxicity Vernonia amygdalina intraperitoneal ethanol extract lipid cardiovascular systemic antioxidant Figures Figure 1 Background Cardiotoxicity is the occurrence of heart dysfunction as electric or muscle damage, resulting in heart toxicity [ 1 ]. This can cause heart failure, arrhythmia, myocarditis, and cardiomyopathy, resulting in a weakened heart that is not as efficient at pumping blood. While some of these effects are reversible, others can cause permanent damage, requiring further treatment [ 2 ]. Cardiotoxicity is considered a subset of systemic toxicity, as it is one of the possible negative effects a drug or substance can have on the body [ 3 ]. Drug-induced cardiotoxicity is a primary concern in both drug development and clinical practice. Although the heart is not a common target for adverse drug reactions, some drugs still cause various adverse cardiac events, which sometimes lead to severe consequences. Direct cardiac toxicity encompasses functional and structural changes of the cardiovascular system due to possible exposure to medicines [ 4 ]. 1, 2- Dimethyl hydrazine (DMH), is a potent colon toxicant, inducing colorectal tumors in experimental animals and is the most widely used model of chemically induced colon toxicity which leads to carcinogenesis [ 5 ]. 1, 2- Dimethyl hydrazine shares many resemblances to human colorectal toxicity, including resemblance in the response to some promotional and preventive agents [ 6 ]. Models used in DMH toxicity studies are developed for exploring the medicinal properties of plant-derived components, because it offers identical site and pathological changes, which can also be found in humans [ 7 ]. Medicinal plants have been serving as precious starting materials for drug development in both developing and developed countries and there has been a great deal of interest nowadays in the role of complementary and alternative medicines for the treatment of many acute and chronic diseases [ 8 ]. Most biologically active compounds isolated from natural plant products have been identified to be nontoxic or less toxic to normal cells, and this has gained attention from the scientific community and clinicians in the present drug discovery era [ 9 ]. Vernonia amygdalina , also known as bitter leaf is a medicinal plant widely used in traditional medicine across various parts of Nigeria. The leaves of this plant which have numerous bioactive compounds, offer a wide range of potential health benefits [ 10 ]. Vernonia amygdalina is rich in biologically-active compounds such as antioxidants and polyphenols which helps to reduce oxidative stress resulting from the accumulation of free radicals, thus leading to the prevention of diseases [ 11 ]. In this study we investigated cardioprotective potentials of Vernonia amygdalina on 1,2-Dimethylhydrazine induced toxicity in rats. Methods Chemicals and Reagents Chemicals, reagents and solvents used in this study were of analytical grade. They were purchased from Sigma-Aldrich Ltd. (St. Lous Mo, USA), Randox Ltd. (UK), and Pyrex Ltd. (Nigeria). They include distilled water, phosphate buffer saline, ethanol, 1, 2 dimethylhydrazine powder, total cholesterol, triacylglycerol, nitric oxide, glutathione reductase, glutathione peroxidase, superoxide dismutase, catalase and malondialdehyde. Equipment and Apparatuses The equipment and apparatuses used in this study includes: micropipette (10 – 50µL and 100 – 10000µL), measuring cylinders, filter papers/cheese cloth, bunsen burner, plain bottles, test tubes, surgical blades, syringes, galvage tubes, cotton wools, methylated spirit, latex hand gloves, spectrophotometer, centrifuge, Soxhlet machine, laboratory fridge and electronic weighing balance. Collection, Identification and Preparation of Vernonia amygdalina Extract Fresh mature leaves of the plant were obtained from a vegetable farm in Benin City, Edo State, Nigeria. They were identified and authenticated in the Herbarium of the Department of Plant Biology and Biotechnology, University of Benin, Nigeria, with the voucher number given as: UBH-V342. Fresh leaves of Vernonia amygdalina were separated from the stalk, washed and air-dried at room temperature (24ᵒC), pulverized, crushed into fine powder and weighed. Ethanol extract of Vernonia amygdalina leaves were prepared by soaking 400g of the dry powdered plant leaves in 1000ml of absolute ethanol at room temperature for 72 hrs. The extract was thereafter filtered first through a Whatmann filter paper No. 42(125mm) and then through cotton wool. The extract was concentrated using a rotary evaporator at 40ºC to one-tenth its original volume and finally with a freeze drier. The dried residue was stored at 4ºC. Portions of the crude plant extract were weighed, dissolved in distilled water and kept for experimental analysis. Experimental Animals Male Wistar albino rats weighing 150 – 200g, were purchased from the animal house, Department of Biochemistry, University of Benin, Benin City. They were accommodated in clean disinfected cages under standard laboratory conditions, with access to feeds (pelletized growers mash) and water ad libitum. They were acclimatized for two (2) weeks before the experiment began. The experimental protocol for this study was conducted following established guidelines as described by the National Institute of Health guidelines in the “Principle of Laboratory Animal Care” (NIH Publication No. 85 − 23) and approved by the Animal Care Ethical Committee of University of Benin, Benin City, Edo State, Nigeria. Experimental Design of the Study Forty (40) male Wistar albino rats weighing 150 – 200 g were randomly assigned to eight (8) groups (5 rats per group) as follows: control, DMH (40 mg/kg body weight), silymarin (100 mg/kg body weight), Vernonia amygdalina (300 mg/kg body weight), pretreatment (200 mg/kg body weight body weight), pretreatment (400 mg/kg body weight), post-treatment (200 mg/kg body weight), and post-treatment (400 mg/kg body weight) groups. With the exception of control and Vernonia amygdalina groups, the rats were exposed to DMH prior to or after treatment with Vernonia amygdalina via intraperitoneal route at a single dose of 40 mg/kg body weight [12]. Rats in silymarin group were treated with the standard hepato-/cardio-protective drug, silymarin (100 mg/kg body weight). The body weight of rats in all groups was recorded at weekly interval for 21 days and treatment lasted for the same period of time. Table 2: Groupings and Treatments EXPERIMENTAL DESIGN Groups Treatments I Control II DMH only (40 mg/kg body weight) III Silymarin (100 mg/kg body weight) IV Vernonia amygdalina leaf extract only (300 mg/kg body weight) V Pretreatment – VA leaf extract (200 mg/kg bwt) for 18 days, then followed by DMH (40 mg/kg body weight). VI Pretreatment – VA leaf extract (400 mg/kg bwt) for 18 days, then followed by DMH (40 mg/kg body weight). VII Post treatment – DMH (40 mg/kg bwt) on day 0, then followed by VA leaf extract (200 mg/kg body weight) for 3 weeks. VIII Post treatment – DMH (40 mg/kg body weight) on day 0, then followed by VA leaf extract (400 mg/kg body weight) for 3 weeks. Blood/Tissue Sample Collection and Preparation At the closing stages of the experiment, blood samples were collected by cardiac puncture under mild ketamine anesthesia into plain and heparin/EDTA containers and centrifuged at 3500rpm for 15min to obtain plasma. The heart tissues were excised and used for histological studies, as well as homogenates preparation. Biochemical analysis were carried out for the following test: High density lipoprotein – cholesterol (HDL-C), Low density lipoprotein – cholesterol (LDL-C), Very low density lipoprotein – cholesterol (VLDL-C), Total cholesterol (TC), Triglyceride (TG), Cardiovascular disease risk factors - [(Atherogenic index of plasmas (AIP), Atherogenic coefficient (AC), Cardiac risk ratio (CRR)], Nitric oxide (NO), Superoxide dismutase (SOD), Catalase (CAT) and Malondialdehyde (MDA), Glutathione (GSH), Glutathione Peroxidase (GPx), Glutathione reductase (GR) and concentration of reduced glutathione (%GSH). Biochemical Analysis Heart tissues were homogenized in ice-cold phosphate buffer using a mechanical grinder. Tissue homogenates were centrifuged at 3,500 rpm in a refrigerated centrifuge at 4 °C for 10 min. Supernatants were aliquots which were stored at 20 °C for later determination of heart parameters of oxidative stress and lipid peroxidation. Measurement of Lipid Profile and Cardiovascular disease risk factors Plasma lipid profile parameters were determined: total cholesterol (TC), triglycerides (TG), and high–density–lipoproteins–cholesterol (HDL-C) assays were performed using the Randox Kit according to the manufacturer’s instructions. Low-density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein-cholesterol (VLDL-C) were calculated from the values of triglycerides, total cholesterol, and HDL as earlier described [13,14,15]. Cardiovascular disease risk factors were determined by calculating the atherogenic index ((TC-HDL)/HDL) and coronary risk index. Measurement of Nitric Oxide Concentration To assess the nitrosative stress, the nitric oxide (NO) content of the heart homogenates was measured using the Griess reaction in which nitric oxide is transformed to nitrite as a more stable metabolite that is then converted to HNO 2 in an acidic environment. HNO 2 then forms a diazonium salt in reaction with sulfanilamide which reacts with N-(1-naphthyl) ethylenediamine to generate an azo dye detectable at 540nm. The NO content of the examined heart specimens was expressed as nmol per mg of protein in the sample [16]. Measurement of Lipid Peroxidation Index Malondialdehyde (MDA) was estimated in heart tissues homogenates supernatants following the Thiobarbituric Acid Reacting Substance (TBARS) assay procedure [17]. 100 µL of supernatant was diluted twenty times in 0.15 M Tris-KCl buffer, and deproteinized with 500 µL trichloroacetic acid (30%). The mixture was centrifuged in a bench top centrifuge at 4000 rpm for 10 min at room temperature. 200 µL of the supernatant was removed into eppendorff tube, followed by addition of 200 µL thiobarbituric acid (0.75%), and the mixture was heated at 80 °C for 1 h. The tubes were cooled by placing on ice, 200 µL was removed into microtitre plate and absorbance measured at 532 nm. The concentration of TBARS in the tissues were expressed as ηmol MDA/ mg protein. Measurement of Oxidative Stress Parameters Superoxide dismutase (SOD) enzyme activity was determined in heart tissues using the autooxidation of adrenaline assay method [18]. Assay for catalase enzyme activity in heart tissue supernatants was determined using the colorimetric assay based on the yellow complex formation with H 2 O 2 and molybdate [19]. Glutathione content of tissue samples was determined as described by [20] . Briefly, heart homogenate (1.0mL) was mixed with 0.1mL of 25% trichloroacetic acid (TCA). The mixture was centrifuged at 5,000×g for 10min to remove precipitate. Supernatant (0.1mL) was mixed with 2mL of 0.6mM DTNB prepared in 0.2M sodium phosphate buffer pH (8.0). Absorbance was read at 412nm. GSH Px activity was determined from the oxidation of NADPH to NADP + in the presence of H 2 O 2 used as a substrate and monitored spectrophotometrically at 340nm for 3 minutes. GSH Px was expressed as (mol of NADPH/min/g protein using an extinction coefficient of 6.22 mM-1 cm-1) for NADPH. Histopathological Examination of Heart Tissues Heart specimens fixed in 10 % phosphosaline were examined microscopically for structural alterations in the tissues at the University of Benin Teaching Hospital (UBTH), Benin City, Edo State, Nigeria. The slides were processed and stained with hematoxylin and eosin (H&E). The photomicrographs of stained slides were captured using Olympus microscope (Olympus, New Jersey, USA) connected through a digital camera to a computer interface. Statistical Analysis Data obtained from this study were expressed as mean ± standard errors of means (SEM). They were evaluated using the one-way analysis of variance (ANOVA). Post-hoc comparison test was carried out using Turkey HSD to evaluate pair-wise differences among group means. Differences between groups were considered significant at p < 0.05. All statistical analysis were performed using the SPSS software tool (Version: 20, IBM Corporation, New York, USA). Results Effect of ethanol extract of V. amygdalina leaves on body weight of rats Results obtained for the body weight of rats as shown in Table 1, indicated that the DMH group recorded significant reductions ( p< 0.05) in body weight when compared with control and the other groups. Consequently, there was a significant increase ( p< 0.05) in body weight of rats in the treatment groups when compared with the DMH group. Furthermore, the silymarin group recorded a significant increase ( p< 0.05) in final body weight when compared with the other groups. Table 1: Body Weight of Rats Groups Initial Weight (g) Final Weight (g) Control 170.87 ± 8.12 a 200.38 ± 14.48 a DMH 195.03 ± 12.01 b 178.95 ± 11.17 b Silymarin 182.39 ± 5.20 c 212.42 ± 13.56 ac VA only 180.44 ± 3.42 c 216.08 ± 11.94 c Pretreatment (200 mg/kg bwt) 170.36 ± 35.09 a 188.86 ± 41.39 d Pretreatment (400 mg/kg bwt) 168.15 ± 34.62 d 187.66 ± 16.35d e Post-Treatment (200 mg/kg bwt) 177.66 ± 6.87 ae 195.44 ± 7.48 f Post-Treatment (400 mg/kg bwt) 166.50 ± 6.47 df 12.37 ag Values are stated as Mean SEM (n=5) For each parameter, values having different superscripts between groups differ significantly (p<0.05). Effect of ethanol extract of V. amygdalina leaves on body weight change in rats As shown in Table 2, there was a percentage decrease ( p< 0.05) in the body weight change of rats in the DMH group when compared with control and the other groups. Furthermore, groups treated with ethanol extract of V. amygdalina leaves, before and after DMH administration recorded percentage increase ( p< 0.05) in the body weight change relative to the DMH group. Table 2: Change in Body Weight of Rats Groups Weight Change (g) % Weight Change (g) Control 29.51 ± 6.36 a 17.27 ± 0.78 a DMH 16.08 ± 0.84 b 8.24 ± 0.06 b Silymarin 30.03 ± 8.36 c 16.46 ± 1.60 c VA only 35.64 ± 8.52 c 19.75 ± 2.49 c Pretreatment (200 mg/kg bwt) 18.50 ± 6.30 b 13.18 ± 0.17 d Pretreatment (400 mg/kg bwt) 41.51 ± 18.27 e 30.04 ± 0.53 e Post-Treatment (200 mg/kg bwt) 17.78 ± 0.61 b 10.00 ± 0.88 c Post-Treatment (400 mg/kg bwt) 38.02 ± 5.90 d ± 0.91 f Values are stated as Mean SEM (n=5) For each parameter, values having different superscripts between groups differ significantly (p<0.05). Effect of Ethanol Extract of V. amygdalina leaves on weight of cardiac tissues The relative weight of the heart tissues in the DMH group revealed significant increase ( p< 0.05) in weight as shown in Table 3 relative to control and the other groups. Consequently, there were insignificant changes ( p< 0.05) in the various groups administered V. amygdalina extract before and after DMH induction when compared especially with silymarin and V. amygdalina groups respectively. Table 3: Relative Weight of Heart in Rats Groups Heart weight (x 10 -3 ) Relative Heart weight (x 10 -3 ) Control 0.60 ± 0.12 a 3.00 ± 0.10 a DMH 0.72 ± 0.03 b 4.00 ± 0.30b Silymarin 0.64 ± 0.04 c 3.00 ± 0.10a VA only 0.68 ± 0.03 a 3.10 ± 0.10a Pretreatment (200 mg/kg bwt) 0.62 ± 0.03 a 3.90 ± 0.20 a, c Pretreatment (400 mg/kg bwt) 0.69 ± 0.03 a 3.80 ± 0.10 a, d Post-Treatment (200 mg/kg bwt) 0.65 ± 0.03 a 3.30 ± 0.30 a, b Post-Treatment (400 mg/kg bwt) 0.61 ± 0.05 a 2.90 ± 0.20 d Values are stated as Mean SEM (n=5) For each parameter, values having different superscripts between groups differ significantly (p<0.05). Effect of Ethanol Extract of V. amygdalina on lipid profile of rats As shown in Table 4 and Table 5, results obtained from the lipid profile of rats in the DMH group recorded a high significant increase ( p< 0.05) in the plasma levels of total cholesterol (TC), triglyceride (TG), very low-density lipoprotein-cholesterol (VLDL-C) and low-density lipoprotein-cholesterol (LDL-C), while high density lipoprotein-cholesterol (HDL-C) was significantly reduced ( p< 0.05) relative to control and the other groups. Consequently, the pre- and post-treatment groups revealed significant decreases ( p< 0.05) in levels of TC, TG, LDL-C and VLDL-C, and an increase ( p< 0.05) in HDL-C levels when compared with the DMH groups. Table 4: Lipid Profile of the Rats Groups Plasma Total Cholesterol (mg/dL) Plasma Triglyceride (mg/dL) HDL-Cholesterol (mg/dL) Control 26.88 ± 3.30 a 42.52 ± 2.01 a 54.38 ± 1.68 a DMH 92.75 ± 0.44 b 93.61 ± 4.56 b 16.01 ± 0.98b Silymarin 47.83 ± 1.68 c 48.54 ± 1.83 a 47.93 ± 0.89 c VA only 42.62 ± 0.18 c 49.09 ± 0.92 a 51.11 ± 2.48 a Pretreatment (200 mg/kg bwt) 50.03 ± 2.00 d 54.32 ± 3.11 a 66.04 ± 4.10 d Pretreatment (400 mg/kg bwt) 54.63 ± 1.14 d 56.01 ± 1.51 a 49.66 ± 4.56 e Post-Treatment (200 mg/kg bwt) 57.03 ± 1.51d 62.41 ± 1.10 c 55.70 ± 2.12 a Post-Treatment (400 mg/kg bwt) 52.52 ± 0.18 d 45.99 ± 17.89 a 49.51 ± 5.66 e Values are stated as Mean SEM (n=5) For each parameter, values having different superscripts between groups differ significantly (p<0.05). Table 5: Lipid Profile of the Rats (Cont’d) Groups Plasma VLDL-Cholesterol (mg/dL LDL- Cholesterol (mg/dL) Control 8.50 ± 1.04 a 44.77 ± 4.02 a DMH 18.72 ± 1.53 b 179.32 ± 7.53 b Silymarin 9.71 ± 1.09 c 111.06 ± 3.84 c VA only 9.82 ± 0.88 c 115.92 ± 4.11c Pretreatment (200 mg/kg bwt) 10.32 ± 0.41 d 59.10 ± 11.56 d Pretreatment (400 mg/kg bwt) 7.51 ± 1.11 e 59.85 ± 8.81 d Post-Treatment (200 mg/kg bwt) 12.48 ± 0.93 b 59.87 ± 2.58 d Post-Treatment (400 mg/kg bwt) 9.20 ± 1.27 c 89.59 ± 2.82 e Values are stated as Mean SEM (n=5) For each parameter, values having different superscripts between groups differ significantly (p<0.05). Effect of ethanol extract of V. amygdalina on cardiovascular disease risk factors of rats In this study, there were high significant increases ( p < 0.05) in the mean values of cardiovascular disease risk factors [atherogenic index of plasma (AIP), atherogenic coefficient (AC), cardiac risk ratio (CRR)], but these parameters were markedly reduced ( p < 0.05) after treatment with ethanol extract of V. amygdalina (Table 6). Table 6: Cardiovascular Disease Risk Factors Groups Atherogenic Index of Plasma Atherogenic Coefficient Cardiac Risk Ratio Control 44.93 ± 2.37 a 0.98 ± 0.06 a 1.98 ± 0.08 a DMH 180.49 ± 8.26 b 12.37 ± 1.16 b 13.37 ± 0.85 b Silymarin 111.26 ± 5.84 c 2.52 ± 0.46 c 3.52 ± 0.28 c VA only 116.11 ± 5.03 c 2.46 ± 0.18 c 3.46 ± 0.56 c Pretreatment (200 mg/kg bwt) 66.04±4.10 d 3.19 ± 0.29 d 2.47 ± 0.64 b Pretreatment (400 mg/kg bwt) 49.66±4.56 a 2.10 ± 9.46 c 2.20 ± 0.82 b Post-Treatment (200 mg/kg bwt) 60.09 ± 1.62 d 1.30 ± 0.09 e 2.30 ± 0.40 b Post-Treatment (400 mg/kg bwt) 89.78 ± 2.84 e 2.00 ± 0.21 c 3.00 ± 0.50 c Values are stated as Mean SEM (n=5) For each parameter, values having different superscripts between groups differ significantly (p<0.05). Effect of ethanol extract of V. amygdalina on the activities of cardiac antioxidant enzymes in rats Exposure of Wistar albino rats to DMH led to significant reductions ( p< 0.05) in the concentrations of cardiac antioxidant enzymes (CAT, SOD, GPx, GSH, GR and % GSH) relative to control and the other groups as shown in Table 7 and Table 8. However, treatment of rats before and after DMH administration with ethanol extract of V. amygdalina significantly increased ( p< 0.05) the levels of the antioxidant enzymes when compared with the DMH group. Table 7: Activities of Antioxidant Enzymes in Cardiac Tissues Groups Catalase (U/min) x 10 -2 SOD (U/min) x 10 -2 GPx (U/min) x 10 -4 Control 41.45 ± 1.25 a 39.00 ± 2.00 a 14.50 ± 0.50 a DMH 11.50 ± 0.10 b 13.50 ± 3.50 b 0.65 ± 0.15 b Silymarin 36.10 ± 1.20 c 28.50 ± 0.50 c 11.50 ± 1.50 c VA only 35.45 ± 0.25 c 25.50 ± 0.50 c 11.00 ± 1.00 c Pretreatment (200 mg/kg bwt) 35.60 ± 1.82 c 24.50 ± 0.50 c 8.00 ± 1.00 d Pretreatment (400 mg/kg bwt) 36.37 ± 1.49 c 30.50 ± 2.50 a 9.00 ± 0.00 e Post-Treatment (200 mg/kg bwt) 36.00 ± 0.90 c 28.50 ± 1.50 c 8.50 ± 0.50 d Post-Treatment (400 mg/kg bwt) 37.70 ± 1.40 c 31.00 ± 4.00 a 9.50 ± 0.50 e Values are stated as Mean SEM (n=5) For each parameter, values having different superscripts between groups differ significantly (p<0.05). Table 8: Glutathione Reductase Activity and Concentration of Reduced Glutathione in Cardiac Tissues Groups GR (U/min) x 10 -3 GSH (mg/mL) % GSH Control 47.50 ± 0.50 a 48.77 ± 0.47 a 72.87 ± 0.46 a DMH 33.00 ± 0.00 b 34.15 ± 0.05 b 38.16 ± 1.32 b Silymarin 44.50 ± 0.50 a 46.77 ± 0.29 a 66.79 ± 1.61 c VA only 43.50 ± 1.50 a 46.75 ± 0.11 a 64.17 ± 2.28 c Pretreatment (200 mg/kg bwt) 44.00 ± 1.00 a 44.93 ± 0.68 a 61.09 ± 4.09 c Pretreatment (400 mg/kg bwt) 45.50 ± 0.50 a 46.54 ± 0.11 a 64.95 ± 3.66 c Post-Treatment (200 mg/kg bwt) 43.00 ± 1.00 a 46.59 ± 1.09 a 53.20 ± 5.14 d Post-Treatment (400 mg/kg bwt) 44.50 ± 0.50 a 47.86 ± 0.44 a 61.35 ± 3.01 c Values are stated as Mean SEM (n=5) For each parameter, values having different superscripts between groups differ significantly (p<0.05). Effect of ethanol extract of V. amygdalina on concentrations of malondialdehyde and nitric oxide in cardiac tissues of rats In this study, there were significant increase ( p< 0.05) in the mean values of cardiac NO and MDA in the DMH group when compared with control and the other groups as shown in Table 9. Consequently, treatment of rats with ethanol extract of V. amygdalina significantly decreased ( p< 0.05) these values close to normal levels (Table 9) Table 9: Levels of Malondialdehyde and Nitric Oxide in Cardiac Tissues Groups MDA (mole/mg tissue) x 10 -3 Nitric Oxide (µmol/L) Control 2.50 ± 0.50 a 36.95 ± 12.55 a DMH 14.50 ± 1.50 b 59.95 ± 2.05 b Silymarin 3.50 ± 0.50 c 30.10 ± 5.40a VA only 2.67 ± 0.33 a 41.80 ± 0.60 c Pretreatment (200 mg/kg bwt) 5.00 ± 1.00 d 40.55 ± 18.25 c Pretreatment (400 mg/kg bwt) 3.67 ± 0.33 c 40.25 ± 3.35 c Post-Treatment (200 mg/kg bwt) 5.00 ± 1.00 d 41.50 ± 0.80 c Post-Treatment (400 mg/kg bwt) 4.00 ± 1.00 e 40.85 ± 1.85 c Values are stated as Mean SEM (n=5) For each parameter, values having different superscripts between groups differ significantly (p<0.05). Heart Discussion In this current research, the rats were exposed to 1, 2 dimethylhydrazine (DMH) before and after Vernonia amygdalina administration. Results obtained for the body weight of rats as shown in Table 1 , indicated that the DMH group recorded significant reductions ( p < 0.05) in the final body weight when compared with control and the other groups. However, there was a significant increase ( p < 0.05) in the relative weight of the heart when compared with other groups as shown in Table 3 . When rats are exposed to toxicants, they typically experience a decrease in body weight when compared to normal rats, meaning the exposure to DMH can lead to weight loss in the animals; this is often used as an indicator of toxicity and is frequently studied in research investigating potential preventive treatments for diseases [ 21 ]. The percentage increases in body weight of rats treated with ethanol extract of V. amygdalina leaves were significantly increased ( p < 0.05), relative to the DMH group as shown in Table 2 . This implies that the extract possesses beneficial properties for weight management. This agrees with a similar study carried out by [ 22 ]. Dyslipidemia is a condition of abnormal lipids, such as high triacylglycerol, cholesterol, and low-density lipoprotein cholesterol levels, which is characterized by metabolic disorders highly associated with obesity [ 23 ]. Lipid profile in plasma and tissues are important diagnostic tools, particularly in conditions such as obesity, diabetes mellitus, coronary heart disease, atherosclerosis, hypertension, infertility, obstructive jaundice, hepatitis and other diseases characterized by abnormalities of lipid metabolism [ 24 ]. Results obtained from the lipid profile of rats in the DMH group as shown in Table 4 and Table 5 , recorded a high significant increase ( p < 0.05) in the plasma levels of total cholesterol (TC), triglyceride (TG), very low-density lipoprotein-cholesterol (VLDL-C) and low-density lipoprotein-cholesterol (LDL-C), while high density lipoprotein-cholesterol (HDL-C) was significantly reduced relative to control and the other groups. This implies that DMH administration can lead to dyslipidemia which is a known condition of abnormal lipids in the body [ 25 ]. Consequently, the pre- and post-treatment groups revealed significant decreases ( p < 0.05) in plasma levels of TC, TG, LDL-C and VLDL-C, and an increase ( p < 0.05) in HDL-C levels when compared to the DMH groups. These observed effects of V. amygdalina in the plasma levels of lipid profile in DMH rats suggest that the extract is effective in ameliorating complications such as cardiovascular disease, arteriosclerosis, coronary artery disease etc. owing to its high content of polyphenols which are bioactive components in the extract [26, 27]. The elevated levels ( p < 0.05) of the cardiovascular disease risk factors [atherogenic index of plasma (AIP), atherogenic coefficient (AC) and cardiac risk ratio (CRR)], in the DMH group as shown in Table 6 , implies that there might be an increased risk of coronary heart disease and arteriosclerosis [ 28 ]. On the other hand, these changes were significantly reverted ( p < 0.05) especially in the pre- and post-treatment groups relative to the control, silymarin and DMH groups respectively. This implies that V. amygdalina can reduce complications of cardiovascular disease such as blood pressure in rats, further contributing to its cardiovascular benefits [ 29 , 30 ]. Antioxidant enzymes are crucial for protecting the body against the damaging effects of reactive oxygen species (ROS) or free radicals. They neutralize these highly reactive molecules, preventing them from causing harm to cells and tissues. By reducing ROS, antioxidant enzymes help maintain a healthy balance in the body, supporting overall well-being [ 31 ]. Exposure of Wistar albino rats to DMH led to significant reductions ( p < 0.05) in the concentrations of cardiac antioxidant enzymes (CAT, SOD, GPx, GSH, GR and % GSH) relative to control and the other groups as shown in Table 7 and Table 8 . The decrease observed in these parameters occurred due to the formation of free radicals caused by oxidative stress thereby leading to decrease in membrane fluidity, cell injury and cell death [ 32 ]. However, treatment of rats before and after DMH administration with ethanol extract of V. amygdalina significantly increased ( p < 0.05) the levels of the antioxidant enzymes when compared with the DMH group. This suggests that the extract relieves heart tissues from inflammation and minimizes oxidative stress and cell injury [ 33 ]. Other studies further shows that the extract contains vitamins and trace elements that promote healing in heart tissue [ 34 ]. In cardiac tissues, elevated levels of both malondialdehyde (MDA) and nitric oxide (NO) can be indicators of oxidative stress and potential heart damage. MDA, a product of lipid peroxidation, reflects oxidative stress, while NO, a vasodilator, can be affected by oxidative stress in the heart [ 35 ]. In this study, there were significant increase ( p < 0.05) in the mean values of cardiac NO and MDA in the DMH group when compared with control and the other groups as shown in Table 9 . The remarkable elevations of these parameters suggests that there is an increase in lipid peroxidation, loss of vascular integrity, coronary artery disease, atherosclerosis, blood pressure and smooth muscle cell proliferation [ 36 ]. Consequently, treatment of rats with ethanol extract of V. amygdalina significantly decreased ( p < 0.05) these values close to normal levels which means that the extract may have protective effects against oxidative stress and inflammation in the heart [ 37 ]. In the histology studies, sections of heart tissues in rats exposed to DMH alone showed severe congestion of blood vessels and derangement of muscle fiber when compared with control and other groups (Plate 1 and Plate 2). Sections of cardiac tissues of rats that received only V. amygdalina and silymarin revealed normal myocytes, coronary artery and mild congestion with peripherally placed nuclei surrounded by normal eosinophilic cytoplasm (Plate 3 and Plate 4). Segments of cardiac muscles of the pre- and post-treatment groups at lower and higher doses revealed moderate myocytes, mild vascular architecture and mild vascular dilation with peripherally placed nuclei surrounded by eosinophilic cytoplasm which is consistent with the control group (Plate 5, Plate 6, Plate 7 and Plate 8). The defects in heart tissue histoarchitecture seen in the DMH group is due to edema, vasoconstriction, severe glassy or waxy hyaline degeneration, and necrosis of skeletal muscles [ 38 ]. V. amygdalina treatment prior to or after DMH induction at lower and higher doses suggests that the extract might have cardioprotective effects in rats, potentially by reducing oxidative stress and apoptosis, and improving heart histology [ 39 ]. This shows that the extract enhances the antioxidant defense system in rats, potentially reducing oxidative stress-induced damage in heart histology [ 40 ]. Conclusion The results of this study have shown that Vernonia amygladina is able to suppress or reduce oxidative stress associated with cardiac toxicity in rats due to phytochemicals such as saponins and polyphenols present in the plant extract. Thus, further research on Vernonia amygladina may reveal its potential as a source of phyto-medicine which can be presented as a recommendation for clinical trials. Abbreviations %GSH – Concentration of Reduced Glutathione AC – Atherogenic coefficient AIP – Atherogenic index of plasmas ANOVA – Analysis of variance AOM – Azoxymethane (AOM) CRR – Cardiac risk ratio CVD – Cardiovascular disease DMH – 1, 2- Dimethyl hydrazine DNA – Deoxyribonucleic Acid EDTA – Ethylenediaminetetraacetic acid GPx – Glutathione Peroxidase GR – Glutathione reductase GSH – Glutathione HDL-C – High Density Lipoprotein Cholesterol LDL-C – Low Density Lipoprotein Cholesterol MDA – Malondialdehyde ROS – Reactive Oxygen Species SEM – Standard Error Mean SOD – Superoxide Dismutase TAG – Triacylglycerol TP – Total Protein UBTH – University of Benin Teaching Hospital VA – Vernonia amygdalina VLDL – Very Low-Density Lipoprotein WHO – World Health Organization Declarations Ethics approval and consent to participate The experimental protocol for this study was approved by the Faculty of Life Science Ethical Committee of University of Benin, Benin City, Edo State, Nigeria. Consent for publication Not applicable Availability of data and material All data generated or analysed during this study are included in this published article [and its supplementary information files]. Competing interests The authors declare that they have no competing interests Funding Not applicable Authors' contributions AOO conceived the idea for the work, Methodology, AOO and ODA designed the study, AO and ODA were involved in carrying out the analysis and interpretation of data generated in this study, AO and ODA provided resources such as assay kits and laboratory equipment for this study, AOO prepared the original draft/manuscript of this work, ODA substantively reviewed and edited the work, ODA approved the submitted version of the work. Acknowledgements Not applicable References Sishi BJN. Chapter 10: Autophagy Upregulation Reduces Doxorubicin-Induced Cardiotoxicity. In: Hayat MA, editors. 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Vernonia amygdalina protects against doxorubicin-induced hepatic and renal damage in rats: mechanistic insights. Pharmacia 2023; 70 (3): 825-835. DOI 10.3897/pharmacia.70.e112425 Ugwoke C, Nzekwe U, Ameh G. Phytochemical constituents and ethnobotany of the leaf extract of bitter leaf (Vernonia amygdalina Del.) Journal of Pharmaceutical and Allied Sciences, 2011;7(3). https://doi.org/10.4314/jophas.v7i3.63409 Plate Plates 3.1 to 3.8 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files floatimage2.jpeg Plate 3.1: Sections of the heart tissues of the control group revealed: A, normal myocytes, B, coronary artery, C, interstitial space with peripherally placed nuclei surrounded by normal eosinophilic cytoplasm. Haematoxylin and eosin. Magnification: x400 floatimage3.jpeg Plate 3.2: Sections of the heart tissues of the DMH group (40mg/kg body weight) shows: A, derangement of myofibers, B, perivascular fibrosis, C, asymmetrical vascular hypertrophy and severe congestion of blood vessels Haematoxylin and eosin. Magnification: x400 floatimage4.jpeg Plate 3.3: Sections of the heart tissues of the silymarin group (100mg/kg body weight) revealed: A, normal myocytes, B, coronary artery, C, interstitial space with peripherally placed nuclei surrounded by normal eosinophilic cytoplasm Haematoxylin and eosin. Magnification: x400 floatimage5.jpeg Plate 3.4: Sections of the heart tissues of the V. amygdalina group revealed: A, normal myocytes, B, coronary artery, C, mild congestion. Haematoxylin and eosin. Magnification: x400 floatimage6.jpeg Plate 3.5: Sections of the heart tissues of the pretreatment group (200mg/kg body weight) revealed: A, normal myocytes, B, vascular architecture, C, mild congestion and dilation. Haematoxylin and eosin. Magnification: x400 floatimage7.jpeg Plate 3.6: Sections of the heart tissues of the pretreatment group (400mg/kg body weight) revealed: A, normal myocytes, B, mild vascular architecture, C, mild vascular dilation. Haematoxylin and eosin. Magnification: x400 floatimage8.jpeg Plate 3.7: Sections of the heart tissues of the post-treatment group (200mg/kg body weight) revealed: A, moderate myocytes, B, peripherally placed nuclei surrounded by normal eosinophilic cytoplasm C, mild vascular dilation. Haematoxylin and eosin. Magnification: x400 floatimage9.jpeg Plate 3.8: Sections of the heart tissues of the post-treatment group (400mg/kg body weight) revealed: A, moderate myocytes, B, peripherally placed nuclei surrounded by normal eosinophilic cytoplasm C, mild vascular dilation. Haematoxylin and eosin. 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08:20:38","extension":"xml","order_by":21,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":149457,"visible":true,"origin":"","legend":"","description":"","filename":"aa2d4b2b9922463ab61f80b4e985cc8a1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8029156/v1/70bfe9d6fc29bd2b2ca91b20.xml"},{"id":95708136,"identity":"0f4b167b-b09b-4746-8145-7c37be929e51","added_by":"auto","created_at":"2025-11-12 07:22:46","extension":"html","order_by":22,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":159824,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8029156/v1/c8b7485af3cea7ad02fe74a2.html"},{"id":95708112,"identity":"2e602cb5-33b1-4563-be5c-df900fca9e6e","added_by":"auto","created_at":"2025-11-12 07:22:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":750703,"visible":true,"origin":"","legend":"\u003cp\u003e(a) \u003cem\u003eVernonia amygdalina\u003c/em\u003eplant (b) Washed bitter leaves\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8029156/v1/5c0f6d9ae8bf48f914d6180c.png"},{"id":96921056,"identity":"60aa6a46-6ac8-4e9d-abeb-4bcd58f48fde","added_by":"auto","created_at":"2025-11-27 14:15:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2843254,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8029156/v1/331a449b-946a-49b8-9464-a781d43c498b.pdf"},{"id":95708108,"identity":"5f286d73-bf04-4cc2-af1c-150593de25f7","added_by":"auto","created_at":"2025-11-12 07:22:46","extension":"jpeg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":488810,"visible":true,"origin":"","legend":"\u003cp\u003ePlate 3.1: Sections of the heart tissues of the control group revealed: A, normal myocytes, B, coronary artery, C, interstitial space with peripherally placed nuclei surrounded by normal eosinophilic cytoplasm.\u003c/p\u003e\n\u003cp\u003eHaematoxylin and eosin. Magnification: x400\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8029156/v1/5187cb4670a10554024ce63d.jpeg"},{"id":95708110,"identity":"74b14fda-905a-448f-a173-97235e568022","added_by":"auto","created_at":"2025-11-12 07:22:46","extension":"jpeg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":495535,"visible":true,"origin":"","legend":"\u003cp\u003ePlate 3.2: Sections of the heart tissues of the DMH group (40mg/kg body weight) shows: \u0026nbsp;A, derangement of myofibers, B, perivascular fibrosis, C, asymmetrical vascular hypertrophy and severe congestion of blood vessels\u003c/p\u003e\n\u003cp\u003eHaematoxylin and eosin. Magnification: x400\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8029156/v1/e7ae4c4a8baec5beb6dcfb79.jpeg"},{"id":95708109,"identity":"12b4964d-685c-469a-ac46-fe9606c9bd89","added_by":"auto","created_at":"2025-11-12 07:22:46","extension":"jpeg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":453606,"visible":true,"origin":"","legend":"\u003cp\u003ePlate 3.3: Sections of the heart tissues of the silymarin group (100mg/kg body weight) revealed: A, normal myocytes, B, coronary artery, C, interstitial space with peripherally placed nuclei surrounded by normal eosinophilic cytoplasm\u003c/p\u003e\n\u003cp\u003eHaematoxylin and eosin. Magnification: x400\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8029156/v1/f43ee391377b920ce6cf4094.jpeg"},{"id":95708113,"identity":"b3394dea-e8a6-40ae-9f79-3018893e729b","added_by":"auto","created_at":"2025-11-12 07:22:46","extension":"jpeg","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":471925,"visible":true,"origin":"","legend":"\u003cp\u003ePlate 3.4: Sections of the heart tissues of the \u003cem\u003eV. amygdalina\u003c/em\u003e group revealed: A, normal myocytes, B, coronary artery, C, mild congestion.\u003c/p\u003e\n\u003cp\u003eHaematoxylin and eosin. Magnification: x400\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8029156/v1/e7dc04ba13e0520f0ca4eff2.jpeg"},{"id":95800119,"identity":"5c7d5947-01f1-4eda-96bf-4bb8b3c79c4a","added_by":"auto","created_at":"2025-11-13 08:21:37","extension":"jpeg","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":484518,"visible":true,"origin":"","legend":"\u003cp\u003ePlate 3.5: Sections of the heart tissues of the pretreatment group (200mg/kg body weight)\u003cstrong\u003e \u003c/strong\u003erevealed: A, normal myocytes, B, vascular architecture, C, mild congestion and dilation.\u003c/p\u003e\n\u003cp\u003eHaematoxylin and eosin. Magnification: x400\u003c/p\u003e","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8029156/v1/2297867e92b8454b8e638ce8.jpeg"},{"id":95800747,"identity":"bef56169-f250-45f6-a254-3900d524de4c","added_by":"auto","created_at":"2025-11-13 08:23:23","extension":"jpeg","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":409781,"visible":true,"origin":"","legend":"\u003cp\u003ePlate 3.6: Sections of the heart tissues of the pretreatment group (400mg/kg body weight)\u003cstrong\u003e \u003c/strong\u003erevealed: A, normal myocytes, B, mild vascular architecture, C, mild vascular dilation.\u003c/p\u003e\n\u003cp\u003eHaematoxylin and eosin. Magnification: x400\u003c/p\u003e","description":"","filename":"floatimage7.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8029156/v1/ee178e0c0741ea7021babaa4.jpeg"},{"id":95800883,"identity":"8380cf38-f8bd-46de-a963-daf6b0f7ff9b","added_by":"auto","created_at":"2025-11-13 08:23:49","extension":"jpeg","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":487072,"visible":true,"origin":"","legend":"\u003cp\u003ePlate 3.7: Sections of the heart tissues of the post-treatment group (200mg/kg body weight)\u003cstrong\u003e \u003c/strong\u003erevealed: A, moderate myocytes, B, peripherally placed nuclei surrounded by normal eosinophilic cytoplasm C, mild vascular dilation.\u003c/p\u003e\n\u003cp\u003eHaematoxylin and eosin. Magnification: x400\u003c/p\u003e","description":"","filename":"floatimage8.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8029156/v1/1cbda397d9e4619034f45822.jpeg"},{"id":95708123,"identity":"0028ea92-c343-49a0-b7d8-d5ece29c462e","added_by":"auto","created_at":"2025-11-12 07:22:46","extension":"jpeg","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":436166,"visible":true,"origin":"","legend":"\u003cp\u003ePlate 3.8: Sections of the heart tissues of the post-treatment group (400mg/kg body weight)\u003cstrong\u003e \u003c/strong\u003erevealed: A, moderate myocytes, B, peripherally placed nuclei surrounded by normal eosinophilic cytoplasm C, mild vascular dilation.\u003c/p\u003e\n\u003cp\u003eHaematoxylin and eosin. Magnification: x400\u003c/p\u003e","description":"","filename":"floatimage9.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8029156/v1/a1b9e17e614f3b8851624bde.jpeg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cardioprotective Potentials of Vernonia amygdalina on 1,2-Dimethylhydrazine Induced Toxicity in Rats","fulltext":[{"header":"Background","content":"\u003cp\u003eCardiotoxicity is the occurrence of heart dysfunction as electric or muscle damage, resulting in heart toxicity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This can cause heart failure, arrhythmia, myocarditis, and cardiomyopathy, resulting in a weakened heart that is not as efficient at pumping blood. While some of these effects are reversible, others can cause permanent damage, requiring further treatment [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Cardiotoxicity is considered a subset of systemic toxicity, as it is one of the possible negative effects a drug or substance can have on the body [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Drug-induced cardiotoxicity is a primary concern in both drug development and clinical practice. Although the heart is not a common target for adverse drug reactions, some drugs still cause various adverse cardiac events, which sometimes lead to severe consequences. Direct cardiac toxicity encompasses functional and structural changes of the cardiovascular system due to possible exposure to medicines [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e1, 2- Dimethyl hydrazine (DMH), is a potent colon toxicant, inducing colorectal tumors in experimental animals and is the most widely used model of chemically induced colon toxicity which leads to carcinogenesis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. 1, 2- Dimethyl hydrazine shares many resemblances to human colorectal toxicity, including resemblance in the response to some promotional and preventive agents [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Models used in DMH toxicity studies are developed for exploring the medicinal properties of plant-derived components, because it offers identical site and pathological changes, which can also be found in humans [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMedicinal plants have been serving as precious starting materials for drug development in both developing and developed countries and there has been a great deal of interest nowadays in the role of complementary and alternative medicines for the treatment of many acute and chronic diseases [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Most biologically active compounds isolated from natural plant products have been identified to be nontoxic or less toxic to normal cells, and this has gained attention from the scientific community and clinicians in the present drug discovery era [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cem\u003eVernonia amygdalina\u003c/em\u003e, also known as bitter leaf is a medicinal plant widely used in traditional medicine across various parts of Nigeria. The leaves of this plant which have numerous bioactive compounds, offer a wide range of potential health benefits [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. \u003cem\u003eVernonia amygdalina\u003c/em\u003e is rich in biologically-active compounds such as antioxidants and polyphenols which helps to reduce oxidative stress resulting from the accumulation of free radicals, thus leading to the prevention of diseases [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In this study we investigated cardioprotective potentials of \u003cem\u003eVernonia amygdalina\u003c/em\u003e on 1,2-Dimethylhydrazine induced toxicity in rats.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eChemicals and Reagents\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChemicals, reagents and solvents used in this study were of analytical grade. They were purchased from Sigma-Aldrich Ltd. (St. Lous Mo, USA), Randox Ltd. (UK), and Pyrex Ltd. (Nigeria). They include distilled water, phosphate buffer saline, ethanol, 1, 2 dimethylhydrazine powder, total cholesterol, triacylglycerol, nitric oxide, glutathione reductase, glutathione peroxidase, superoxide dismutase, catalase and malondialdehyde.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEquipment and Apparatuses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe equipment and apparatuses used in this study includes: micropipette (10 \u0026ndash; 50\u0026micro;L and 100 \u0026ndash; 10000\u0026micro;L), measuring cylinders, filter papers/cheese cloth, bunsen burner, plain bottles, test tubes, surgical blades, syringes, galvage tubes, cotton wools, methylated spirit, latex hand gloves, spectrophotometer, centrifuge, Soxhlet machine, laboratory fridge and electronic weighing balance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCollection, Identification and Preparation of \u003cem\u003eVernonia amygdalina\u0026nbsp;\u003c/em\u003eExtract\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFresh mature leaves of the plant were obtained from a vegetable farm in Benin City, Edo State, Nigeria. They were identified and authenticated in the Herbarium of the Department of Plant Biology and Biotechnology, University of Benin, Nigeria, with the voucher number given as: UBH-V342. Fresh leaves of \u003cem\u003eVernonia amygdalina\u0026nbsp;\u003c/em\u003ewere separated from the stalk, washed and air-dried at room temperature (24ᵒC), pulverized, crushed into fine powder and weighed. Ethanol extract of \u003cem\u003eVernonia amygdalina\u0026nbsp;\u003c/em\u003eleaves were prepared by soaking 400g of the dry powdered plant leaves in 1000ml of absolute ethanol at room temperature for 72 hrs. The extract was thereafter filtered first through a Whatmann filter paper No. 42(125mm) and then through cotton wool. The extract was concentrated using a rotary evaporator at 40\u0026ordm;C to one-tenth its original volume and finally with a freeze drier. The dried residue was stored at 4\u0026ordm;C. Portions of the crude plant extract were weighed, dissolved in distilled water and kept for experimental analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExperimental Animals\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMale Wistar albino rats weighing 150 \u0026ndash; 200g, were purchased from the animal house, Department of Biochemistry, University of Benin, Benin City. They were accommodated in clean disinfected cages under standard laboratory conditions, with access to feeds (pelletized growers mash) and water ad libitum. They were acclimatized for two (2) weeks before the experiment began. The experimental protocol for this study was conducted following established guidelines as described by the National Institute of Health guidelines in the \u0026ldquo;Principle of Laboratory Animal Care\u0026rdquo; (NIH Publication No. 85\u0026thinsp;\u0026minus;\u0026thinsp;23)\u0026nbsp;and approved by the Animal Care Ethical Committee of University of Benin, Benin City, Edo State, Nigeria.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExperimental Design of the Study\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eForty (40) male Wistar albino rats weighing 150 \u0026ndash; 200 g were randomly assigned to eight (8) groups (5 rats per group) as follows: control, DMH (40 mg/kg body weight), silymarin (100 mg/kg body weight), \u003cem\u003eVernonia amygdalina\u0026nbsp;\u003c/em\u003e(300 mg/kg body weight), pretreatment (200 mg/kg body weight body weight), pretreatment (400 mg/kg body weight), post-treatment (200 mg/kg body weight), and post-treatment (400 mg/kg body weight) groups. With the exception of control and \u003cem\u003eVernonia amygdalina\u003c/em\u003e groups, the rats were exposed to DMH prior to or after treatment with \u003cem\u003eVernonia amygdalina\u0026nbsp;\u003c/em\u003evia intraperitoneal route at a single dose of 40 mg/kg body weight [12]. Rats in silymarin group were treated with the standard hepato-/cardio-protective drug, silymarin (100 mg/kg body weight). The body weight of rats in all groups was recorded at weekly interval for 21 days and treatment lasted for the same period of time.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2:\u003c/strong\u003e \u003cstrong\u003eGroupings and Treatments \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEXPERIMENTAL DESIGN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18.843%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81.157%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatments\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18.843%;\"\u003e\n \u003cp\u003eI\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81.157%;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18.843%;\"\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81.157%;\"\u003e\n \u003cp\u003eDMH only (40 mg/kg body weight)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18.843%;\"\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81.157%;\"\u003e\n \u003cp\u003eSilymarin (100 mg/kg body weight)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18.843%;\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81.157%;\"\u003e\n \u003cp\u003e\u003cem\u003eVernonia amygdalina\u0026nbsp;\u003c/em\u003eleaf extract only (300 mg/kg body weight)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18.843%;\"\u003e\n \u003cp\u003eV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81.157%;\"\u003e\n \u003cp\u003ePretreatment \u0026ndash; \u003cem\u003eVA\u0026nbsp;\u003c/em\u003eleaf extract (200 mg/kg bwt) for 18 days, then followed by DMH (40 mg/kg body weight).\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18.843%;\"\u003e\n \u003cp\u003eVI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81.157%;\"\u003e\n \u003cp\u003ePretreatment \u0026ndash; \u003cem\u003eVA\u0026nbsp;\u003c/em\u003eleaf extract (400 mg/kg bwt) for 18 days, then followed by DMH (40 mg/kg body weight).\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18.843%;\"\u003e\n \u003cp\u003eVII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81.157%;\"\u003e\n \u003cp\u003ePost treatment \u0026ndash; DMH (40 mg/kg bwt) on day 0, then followed by\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eVA\u0026nbsp;\u003c/em\u003eleaf extract (200 mg/kg body weight) for 3 weeks.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 18.843%;\"\u003e\n \u003cp\u003eVIII\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 81.157%;\"\u003e\n \u003cp\u003ePost treatment \u0026ndash; DMH (40 mg/kg body weight) on day 0, then followed by\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eVA\u0026nbsp;\u003c/em\u003eleaf extract (400 mg/kg body weight) for 3 weeks.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eBlood/Tissue Sample Collection and Preparation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt the closing stages of the experiment, blood samples were collected by cardiac puncture under mild ketamine anesthesia into plain and heparin/EDTA containers and centrifuged at 3500rpm for 15min to obtain plasma. The heart tissues were excised and used for histological studies, as well as homogenates preparation. Biochemical analysis were carried out for the following test: High density lipoprotein \u0026ndash; cholesterol (HDL-C), Low density lipoprotein \u0026ndash; cholesterol (LDL-C), Very low density lipoprotein \u0026ndash; cholesterol (VLDL-C), Total cholesterol (TC), Triglyceride (TG), Cardiovascular disease risk factors - [(Atherogenic index of plasmas (AIP), Atherogenic coefficient (AC), Cardiac risk ratio (CRR)], Nitric oxide (NO), Superoxide dismutase (SOD), Catalase (CAT) and Malondialdehyde (MDA), Glutathione (GSH), Glutathione Peroxidase (GPx), Glutathione reductase (GR) and concentration of reduced glutathione (%GSH).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBiochemical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHeart tissues were homogenized in ice-cold phosphate buffer using a mechanical grinder. Tissue homogenates were centrifuged at 3,500\u0026nbsp;rpm in a refrigerated centrifuge at 4\u0026nbsp;\u0026deg;C for 10\u0026nbsp;min. Supernatants were aliquots which were stored at 20\u0026nbsp;\u0026deg;C for later determination of heart parameters of oxidative stress and lipid peroxidation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeasurement of Lipid Profile and Cardiovascular disease risk factors\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePlasma lipid profile parameters were determined: total cholesterol (TC), triglycerides (TG), and high\u0026ndash;density\u0026ndash;lipoproteins\u0026ndash;cholesterol (HDL-C) assays were performed using the Randox Kit according to the manufacturer\u0026rsquo;s instructions. Low-density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein-cholesterol (VLDL-C) were calculated from the values of triglycerides, total cholesterol, and HDL as earlier described [13,14,15]. Cardiovascular disease risk factors were determined by calculating the atherogenic index ((TC-HDL)/HDL) and coronary risk index.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeasurement of Nitric Oxide Concentration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo assess the nitrosative stress, the nitric oxide (NO) content of the heart homogenates was measured using the Griess reaction in which nitric oxide is transformed to nitrite as a more stable metabolite that is then converted to HNO\u003csub\u003e2\u003c/sub\u003e in an acidic environment. HNO\u003csub\u003e2\u003c/sub\u003e then forms a diazonium salt in reaction with sulfanilamide which reacts with N-(1-naphthyl) ethylenediamine to generate an azo dye detectable at 540nm. The NO content of the examined heart specimens was expressed as nmol per mg of protein in the sample [16].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeasurement of Lipid Peroxidation Index\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMalondialdehyde (MDA) was estimated in heart tissues homogenates supernatants following the Thiobarbituric Acid Reacting Substance (TBARS) assay procedure [17]. 100 \u0026micro;L of supernatant was diluted twenty times in 0.15\u0026nbsp;M Tris-KCl buffer, and deproteinized with 500 \u0026micro;L trichloroacetic acid (30%). The mixture was centrifuged in a bench top centrifuge at 4000\u0026nbsp;rpm for 10\u0026nbsp;min at room temperature. 200 \u0026micro;L of the supernatant was removed into eppendorff tube, followed by addition of 200 \u0026micro;L thiobarbituric acid (0.75%), and the mixture was heated at 80\u0026nbsp;\u0026deg;C for 1\u0026nbsp;h. The tubes were cooled by placing on ice, 200 \u0026micro;L was removed into microtitre plate and absorbance measured at 532\u0026nbsp;nm. The concentration of TBARS in the tissues were expressed as \u0026eta;mol MDA/ mg protein.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeasurement of Oxidative Stress Parameters\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSuperoxide dismutase (SOD) enzyme activity was determined in heart tissues using the autooxidation of adrenaline assay method [18]. Assay for catalase enzyme activity in heart tissue supernatants was determined using the colorimetric assay based on the yellow complex formation with H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e and molybdate [19]. Glutathione content of tissue samples was determined as described by [20]\u003cem\u003e.\u0026nbsp;\u003c/em\u003eBriefly, heart homogenate (1.0mL) was mixed with 0.1mL of 25% trichloroacetic acid (TCA). The mixture was centrifuged at 5,000\u0026times;g for 10min to remove precipitate. Supernatant (0.1mL) was mixed with 2mL of 0.6mM DTNB prepared in 0.2M sodium phosphate buffer pH (8.0). Absorbance was read at 412nm. GSH Px activity was determined from the oxidation of NADPH to NADP\u003csup\u003e+\u003c/sup\u003e in the presence of H\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e used as a substrate and monitored spectrophotometrically at 340nm for 3 minutes. GSH Px was expressed as (mol of NADPH/min/g protein using an extinction coefficient of 6.22 mM-1 cm-1) for NADPH.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHistopathological Examination of Heart Tissues\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHeart specimens fixed in 10 % phosphosaline were examined microscopically for structural alterations in the tissues at the University of Benin Teaching Hospital (UBTH), Benin City, Edo State, Nigeria. The slides were processed and stained with hematoxylin and eosin (H\u0026amp;E). The photomicrographs of stained slides were captured using Olympus microscope (Olympus, New Jersey, USA) connected through a digital camera to a computer interface.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData obtained from this study were expressed as mean \u0026plusmn; standard errors of means (SEM). They were evaluated using the one-way analysis of variance (ANOVA). Post-hoc comparison test was carried out using Turkey HSD to evaluate pair-wise differences among group means. Differences between groups were considered significant at p \u0026lt; 0.05. All statistical analysis were performed using the SPSS software tool (Version: 20, IBM Corporation, New York, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eEffect of ethanol extract of \u003cem\u003eV. amygdalina\u003c/em\u003e leaves on body weight of rats\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResults obtained for the body weight of rats as shown in Table 1, indicated that the DMH group recorded significant reductions (\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) in body weight when compared with control and the other groups. Consequently, there was a significant increase\u0026nbsp;(\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) in body weight of rats in the treatment groups when compared with the DMH group. Furthermore, the silymarin group recorded\u0026nbsp;a significant increase (\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) in final body weight when compared with the other groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTable 1: Body Weight of Rats\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.7755%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInitial Weight (g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFinal Weight (g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.7755%;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e170.87 \u0026plusmn; 8.12\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e200.38 \u0026plusmn; 14.48\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.7755%;\"\u003e\n \u003cp\u003eDMH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e195.03 \u0026plusmn; 12.01\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e178.95 \u0026plusmn; 11.17\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.7755%;\"\u003e\n \u003cp\u003eSilymarin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e182.39 \u0026plusmn; 5.20\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e212.42 \u0026plusmn; 13.56\u003csup\u003eac\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.7755%;\"\u003e\n \u003cp\u003eVA only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e180.44 \u0026plusmn; 3.42\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e216.08 \u0026plusmn; 11.94\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.7755%;\"\u003e\n \u003cp\u003ePretreatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e170.36 \u0026plusmn; 35.09\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e188.86 \u0026plusmn; 41.39\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.7755%;\"\u003e\n \u003cp\u003ePretreatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e168.15 \u0026plusmn; 34.62\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e187.66 \u0026plusmn; 16.35d\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.7755%;\"\u003e\n \u003cp\u003ePost-Treatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e177.66 \u0026plusmn; 6.87\u003csup\u003eae\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e195.44 \u0026plusmn; 7.48\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38.7755%;\"\u003e\n \u003cp\u003ePost-Treatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003cp\u003e166.50 \u0026plusmn; 6.47\u003csup\u003edf\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.6122%;\"\u003e\n \u003col start=\"204\"\u003e\n \u003cli\u003e12.37\u003csup\u003eag\u003c/sup\u003e\u003c/li\u003e\n \u003c/ol\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eValues are stated as Mean\u0026nbsp;\u003c/em\u003e\u003cimg width=\"10\" height=\"18\" src=\"https://myfiles.space/user_files/58895_8739fc6c57c1c19a/58895_custom_files/img1762931184.png\" alt=\"image\"\u003e\u003cem\u003e\u0026nbsp;SEM (n=5)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFor each parameter, values having different superscripts between groups differ significantly (p\u0026lt;0.05).\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of ethanol extract of \u003cem\u003eV. amygdalina\u003c/em\u003e leaves on body weight change in rats\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table 2, there was a percentage decrease (\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) in the body weight change of rats in the DMH group when compared with control and the other groups. Furthermore, groups treated with ethanol extract of \u003cem\u003eV. amygdalina\u0026nbsp;\u003c/em\u003eleaves, before and after DMH administration recorded percentage increase (\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) in the body weight change relative to the DMH group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTable 2: Change in Body Weight of Rats\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43.75%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0833%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeight Change (g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e% Weight Change (g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43.75%;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0833%;\"\u003e\n \u003cp\u003e29.51 \u0026plusmn; 6.36\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003e17.27 \u0026plusmn; 0.78\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43.75%;\"\u003e\n \u003cp\u003eDMH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0833%;\"\u003e\n \u003cp\u003e16.08 \u0026plusmn; 0.84\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003e8.24 \u0026plusmn; 0.06\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43.75%;\"\u003e\n \u003cp\u003eSilymarin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0833%;\"\u003e\n \u003cp\u003e30.03 \u0026plusmn; 8.36\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003e16.46 \u0026plusmn; 1.60\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43.75%;\"\u003e\n \u003cp\u003eVA only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0833%;\"\u003e\n \u003cp\u003e35.64 \u0026plusmn; 8.52\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003e19.75 \u0026plusmn; 2.49\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43.75%;\"\u003e\n \u003cp\u003ePretreatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0833%;\"\u003e\n \u003cp\u003e18.50 \u0026plusmn; 6.30\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003e13.18 \u0026plusmn; 0.17\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43.75%;\"\u003e\n \u003cp\u003ePretreatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0833%;\"\u003e\n \u003cp\u003e41.51 \u0026plusmn; 18.27\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003e30.04 \u0026plusmn; 0.53\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43.75%;\"\u003e\n \u003cp\u003ePost-Treatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0833%;\"\u003e\n \u003cp\u003e17.78 \u0026plusmn; 0.61\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003cp\u003e10.00 \u0026plusmn; 0.88\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43.75%;\"\u003e\n \u003cp\u003ePost-Treatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0833%;\"\u003e\n \u003cp\u003e38.02 \u0026plusmn; 5.90\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.1667%;\"\u003e\n \u003col start=\"22\"\u003e\n \u003cli\u003e\u0026nbsp;\u0026plusmn; 0.91\u003csup\u003ef\u003c/sup\u003e\u003c/li\u003e\n \u003c/ol\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cem\u003eValues are stated as Mean\u0026nbsp;\u003c/em\u003e\u003cimg width=\"10\" height=\"18\" src=\"https://myfiles.space/user_files/58895_8739fc6c57c1c19a/58895_custom_files/img176293118444.png\" alt=\"image\"\u003e\u003cem\u003e\u0026nbsp;SEM (n=5)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFor each parameter, values having different superscripts between groups differ significantly\u003c/em\u003e \u003cem\u003e(p\u0026lt;0.05).\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of Ethanol Extract of \u003cem\u003eV. amygdalina\u003c/em\u003e leaves on weight of cardiac tissues\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe relative weight of the heart tissues in the DMH group revealed significant increase (\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) in weight as shown in Table 3 relative to control and the other groups. Consequently, there were insignificant changes (\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) in the various groups administered \u003cem\u003eV. amygdalina\u003c/em\u003e extract before and after DMH induction when compared especially with silymarin and \u003cem\u003eV. amygdalina\u0026nbsp;\u003c/em\u003egroups respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Relative Weight of Heart in Rats\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"576\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 39.5833%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHeart weight\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(x 10\u003csup\u003e-3\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRelative Heart weight\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(x 10\u003csup\u003e-3\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 39.5833%;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e0.60 \u0026plusmn; 0.12\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e3.00 \u0026plusmn; 0.10\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 39.5833%;\"\u003e\n \u003cp\u003eDMH\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e0.72 \u0026plusmn; 0.03\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e4.00 \u0026plusmn; 0.30b\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 39.5833%;\"\u003e\n \u003cp\u003eSilymarin\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e0.64 \u0026plusmn; 0.04\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e3.00 \u0026plusmn; 0.10a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 39.5833%;\"\u003e\n \u003cp\u003eVA only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e0.68 \u0026plusmn; 0.03\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e3.10 \u0026plusmn; 0.10a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 39.5833%;\"\u003e\n \u003cp\u003ePretreatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e0.62 \u0026plusmn; 0.03\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e3.90 \u0026plusmn; 0.20\u003csup\u003ea, c\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 39.5833%;\"\u003e\n \u003cp\u003ePretreatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e0.69 \u0026plusmn; 0.03\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e3.80 \u0026plusmn; 0.10\u003csup\u003ea, d\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 39.5833%;\"\u003e\n \u003cp\u003ePost-Treatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e0.65 \u0026plusmn; 0.03\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e3.30 \u0026plusmn; 0.30\u003csup\u003ea, b\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 39.5833%;\"\u003e\n \u003cp\u003ePost-Treatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e0.61 \u0026plusmn; 0.05\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.2083%;\"\u003e\n \u003cp\u003e2.90 \u0026plusmn; 0.20\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cem\u003eValues are stated as Mean\u0026nbsp;\u003c/em\u003e\u003cimg width=\"10\" height=\"18\" src=\"https://myfiles.space/user_files/58895_8739fc6c57c1c19a/58895_custom_files/img1762931185.png\" alt=\"image\"\u003e\u003cem\u003e\u0026nbsp;SEM (n=5)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFor each parameter, values having different superscripts between groups differ significantly (p\u0026lt;0.05).\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of Ethanol Extract of \u003cem\u003eV. amygdalina\u003c/em\u003e on\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003elipid profile of rats\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table 4 and Table 5, results obtained from the lipid profile of rats in the DMH group recorded a high significant increase (\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) in the plasma levels of total cholesterol (TC), triglyceride (TG), very low-density lipoprotein-cholesterol (VLDL-C) and low-density lipoprotein-cholesterol (LDL-C), while high density lipoprotein-cholesterol (HDL-C) was significantly reduced (\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) relative to control and the other groups. Consequently, the pre- and post-treatment groups revealed significant decreases (\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) in levels of TC, TG, LDL-C and VLDL-C, and an increase (\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) in HDL-C levels when compared with the DMH groups.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4: Lipid Profile of the Rats\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"588\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40.8163%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.449%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlasma\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Cholesterol (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlasma Triglyceride (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHDL-Cholesterol (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40.8163%;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.449%;\"\u003e\n \u003cp\u003e26.88 \u0026plusmn; 3.30\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e42.52 \u0026plusmn; 2.01\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e54.38 \u0026plusmn; 1.68\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40.8163%;\"\u003e\n \u003cp\u003eDMH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.449%;\"\u003e\n \u003cp\u003e92.75 \u0026plusmn; 0.44\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e93.61 \u0026plusmn; 4.56\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e16.01 \u0026plusmn; 0.98b\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40.8163%;\"\u003e\n \u003cp\u003eSilymarin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.449%;\"\u003e\n \u003cp\u003e47.83 \u0026plusmn; 1.68\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e48.54 \u0026plusmn; 1.83\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e47.93 \u0026plusmn; 0.89\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40.8163%;\"\u003e\n \u003cp\u003eVA only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.449%;\"\u003e\n \u003cp\u003e42.62 \u0026plusmn; 0.18\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e49.09 \u0026plusmn; 0.92\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e51.11 \u0026plusmn; 2.48\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40.8163%;\"\u003e\n \u003cp\u003ePretreatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.449%;\"\u003e\n \u003cp\u003e50.03 \u0026plusmn; 2.00\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e54.32 \u0026plusmn; 3.11\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e66.04 \u0026plusmn; 4.10\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40.8163%;\"\u003e\n \u003cp\u003ePretreatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.449%;\"\u003e\n \u003cp\u003e54.63 \u0026plusmn; 1.14\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e56.01 \u0026plusmn; 1.51\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e49.66 \u0026plusmn; 4.56\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40.8163%;\"\u003e\n \u003cp\u003ePost-Treatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.449%;\"\u003e\n \u003cp\u003e57.03 \u0026plusmn; 1.51d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e62.41 \u0026plusmn; 1.10\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e55.70 \u0026plusmn; 2.12\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40.8163%;\"\u003e\n \u003cp\u003ePost-Treatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.449%;\"\u003e\n \u003cp\u003e52.52 \u0026plusmn; 0.18\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e45.99 \u0026plusmn; 17.89\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3673%;\"\u003e\n \u003cp\u003e49.51 \u0026plusmn; 5.66\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cem\u003eValues are stated as Mean\u0026nbsp;\u003c/em\u003e\u003cimg width=\"10\" height=\"18\" src=\"https://myfiles.space/user_files/58895_8739fc6c57c1c19a/58895_custom_files/img176293118480.png\" alt=\"image\"\u003e\u003cem\u003e\u0026nbsp;SEM (n=5)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFor each parameter, values having different superscripts between groups differ significantly (p\u0026lt;0.05).\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5: Lipid Profile of the Rats (Cont\u0026rsquo;d)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"510\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 47.0588%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 28.2353%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlasma\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eVLDL-Cholesterol (mg/dL\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24.7059%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDL- Cholesterol (mg/dL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 47.0588%;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0588%;\"\u003e\n \u003cp\u003e8.50 \u0026plusmn; 1.04\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 25.8824%;\"\u003e\n \u003cp\u003e44.77 \u0026plusmn; 4.02\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 47.0588%;\"\u003e\n \u003cp\u003eDMH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0588%;\"\u003e\n \u003cp\u003e18.72 \u0026plusmn; 1.53\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 25.8824%;\"\u003e\n \u003cp\u003e179.32 \u0026plusmn; 7.53\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 47.0588%;\"\u003e\n \u003cp\u003eSilymarin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0588%;\"\u003e\n \u003cp\u003e9.71 \u0026plusmn; 1.09\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 25.8824%;\"\u003e\n \u003cp\u003e111.06 \u0026plusmn; 3.84\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 47.0588%;\"\u003e\n \u003cp\u003eVA only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0588%;\"\u003e\n \u003cp\u003e9.82 \u0026plusmn; 0.88\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 25.8824%;\"\u003e\n \u003cp\u003e115.92 \u0026plusmn; 4.11c\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 47.0588%;\"\u003e\n \u003cp\u003ePretreatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0588%;\"\u003e\n \u003cp\u003e10.32 \u0026plusmn; 0.41\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 25.8824%;\"\u003e\n \u003cp\u003e59.10 \u0026plusmn; 11.56\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 47.0588%;\"\u003e\n \u003cp\u003ePretreatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0588%;\"\u003e\n \u003cp\u003e7.51 \u0026plusmn; 1.11\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 25.8824%;\"\u003e\n \u003cp\u003e59.85 \u0026plusmn; 8.81\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 47.0588%;\"\u003e\n \u003cp\u003ePost-Treatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0588%;\"\u003e\n \u003cp\u003e12.48 \u0026plusmn; 0.93\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 25.8824%;\"\u003e\n \u003cp\u003e59.87 \u0026plusmn; 2.58\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 47.0588%;\"\u003e\n \u003cp\u003ePost-Treatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 27.0588%;\"\u003e\n \u003cp\u003e9.20 \u0026plusmn; 1.27\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 25.8824%;\"\u003e\n \u003cp\u003e89.59 \u0026plusmn; 2.82\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 47.0588%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 27.0588%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 1.17647%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 24.7059%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eValues are stated as Mean\u0026nbsp;\u003c/em\u003e\u003cimg width=\"10\" height=\"18\" src=\"https://myfiles.space/user_files/58895_8739fc6c57c1c19a/58895_custom_files/img176293118452.png\" alt=\"image\"\u003e\u003cem\u003e\u0026nbsp;SEM (n=5)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFor each parameter, values having different superscripts between groups differ significantly (p\u0026lt;0.05).\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of ethanol extract of \u003cem\u003eV. amygdalina\u003c/em\u003e on\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ecardiovascular disease risk factors of rats\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, there were high significant increases (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05) in the mean values of cardiovascular disease risk factors [atherogenic index of plasma (AIP), atherogenic coefficient (AC), cardiac risk ratio (CRR)], but these parameters were markedly reduced (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05) after treatment with ethanol extract of \u003cem\u003eV. amygdalina\u003c/em\u003e (Table 6).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6: Cardiovascular Disease Risk Factors\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"600\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAtherogenic Index of Plasma\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 22%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAtherogenic Coefficient\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCardiac Risk Ratio\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e44.93 \u0026plusmn; 2.37\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21%;\"\u003e\n \u003cp\u003e0.98 \u0026plusmn; 0.06\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18%;\"\u003e\n \u003cp\u003e1.98 \u0026plusmn; 0.08\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003eDMH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e180.49 \u0026plusmn; 8.26\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21%;\"\u003e\n \u003cp\u003e12.37 \u0026plusmn; 1.16\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18%;\"\u003e\n \u003cp\u003e13.37 \u0026plusmn; 0.85\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003eSilymarin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e111.26 \u0026plusmn; 5.84\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21%;\"\u003e\n \u003cp\u003e2.52 \u0026plusmn; 0.46\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18%;\"\u003e\n \u003cp\u003e3.52 \u0026plusmn; 0.28\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003eVA only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e116.11 \u0026plusmn; 5.03\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21%;\"\u003e\n \u003cp\u003e2.46 \u0026plusmn; 0.18\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18%;\"\u003e\n \u003cp\u003e3.46 \u0026plusmn; 0.56\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003ePretreatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e66.04\u0026plusmn;4.10\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21%;\"\u003e\n \u003cp\u003e3.19 \u0026plusmn; 0.29\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18%;\"\u003e\n \u003cp\u003e2.47 \u0026plusmn; 0.64\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003ePretreatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e49.66\u0026plusmn;4.56\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21%;\"\u003e\n \u003cp\u003e2.10 \u0026plusmn; 9.46\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18%;\"\u003e\n \u003cp\u003e2.20 \u0026plusmn; 0.82\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003ePost-Treatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e60.09 \u0026plusmn; 1.62\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21%;\"\u003e\n \u003cp\u003e1.30 \u0026plusmn; 0.09\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18%;\"\u003e\n \u003cp\u003e2.30 \u0026plusmn; 0.40\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003ePost-Treatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e89.78 \u0026plusmn; 2.84\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21%;\"\u003e\n \u003cp\u003e2.00 \u0026plusmn; 0.21\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 18%;\"\u003e\n \u003cp\u003e3.00 \u0026plusmn; 0.50\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 21%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 1%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 17%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eValues are stated as Mean\u0026nbsp;\u003c/em\u003e\u003cimg width=\"10\" height=\"18\" src=\"https://myfiles.space/user_files/58895_8739fc6c57c1c19a/58895_custom_files/img176293118547.png\" alt=\"image\"\u003e\u003cem\u003e\u0026nbsp;SEM (n=5)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFor each parameter, values having different superscripts between groups differ significantly (p\u0026lt;0.05).\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of ethanol extract of \u003cem\u003eV. amygdalina\u003c/em\u003e on the activities of cardiac antioxidant enzymes\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ein rats\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eExposure of Wistar albino rats to DMH led to significant reductions (\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) in the concentrations of cardiac antioxidant enzymes (CAT, SOD, GPx, GSH, GR and % GSH) relative to control and the other groups as shown in Table 7 and Table 8. However, treatment of rats before and after DMH administration with ethanol extract of \u003cem\u003eV. amygdalina\u003c/em\u003e significantly increased (\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) the levels of the antioxidant enzymes when compared with the DMH group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 7: Activities of Antioxidant Enzymes in Cardiac Tissues\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"600\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCatalase (U/min)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ex 10\u003csup\u003e-2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSOD (U/min)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ex 10\u003csup\u003e-2\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGPx (U/min)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ex 10\u003csup\u003e-4\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24%;\"\u003e\n \u003cp\u003e41.45 \u0026plusmn; 1.25\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e39.00 \u0026plusmn; 2.00\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e14.50 \u0026plusmn; 0.50\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003eDMH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24%;\"\u003e\n \u003cp\u003e11.50 \u0026plusmn; 0.10\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e13.50 \u0026plusmn; 3.50\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e0.65 \u0026plusmn; 0.15\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003eSilymarin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24%;\"\u003e\n \u003cp\u003e36.10 \u0026plusmn; 1.20\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e28.50 \u0026plusmn; 0.50\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e11.50 \u0026plusmn; 1.50\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003eVA only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24%;\"\u003e\n \u003cp\u003e35.45 \u0026plusmn; 0.25\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e25.50 \u0026plusmn; 0.50\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e11.00 \u0026plusmn; 1.00\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003ePretreatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24%;\"\u003e\n \u003cp\u003e35.60 \u0026plusmn; 1.82\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e24.50 \u0026plusmn; 0.50\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e8.00 \u0026plusmn; 1.00\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003ePretreatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24%;\"\u003e\n \u003cp\u003e36.37 \u0026plusmn; 1.49\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e30.50 \u0026plusmn; 2.50\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e9.00 \u0026plusmn; 0.00\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003ePost-Treatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24%;\"\u003e\n \u003cp\u003e36.00 \u0026plusmn; 0.90\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e28.50 \u0026plusmn; 1.50\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e8.50 \u0026plusmn; 0.50\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 38%;\"\u003e\n \u003cp\u003ePost-Treatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24%;\"\u003e\n \u003cp\u003e37.70 \u0026plusmn; 1.40\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20%;\"\u003e\n \u003cp\u003e31.00 \u0026plusmn; 4.00\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e9.50 \u0026plusmn; 0.50\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eValues are stated as Mean\u0026nbsp;\u003c/em\u003e\u003cimg width=\"10\" height=\"18\" src=\"https://myfiles.space/user_files/58895_8739fc6c57c1c19a/58895_custom_files/img176293118599.png\" alt=\"image\"\u003e\u003cem\u003e\u0026nbsp;SEM (n=5)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFor each parameter, values having different superscripts between groups differ significantly (p\u0026lt;0.05).\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 8: Glutathione Reductase Activity and Concentration of Reduced Glutathione in Cardiac Tissues\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"600\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGR (U/min)\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;x 10\u003csup\u003e-3\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGSH (mg/mL)\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e% GSH\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e47.50 \u0026plusmn; 0.50\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19%;\"\u003e\n \u003cp\u003e48.77 \u0026plusmn; 0.47\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e72.87 \u0026plusmn; 0.46\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003eDMH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e33.00 \u0026plusmn; 0.00\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19%;\"\u003e\n \u003cp\u003e34.15 \u0026plusmn; 0.05\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e38.16 \u0026plusmn; 1.32\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003eSilymarin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e44.50 \u0026plusmn; 0.50\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19%;\"\u003e\n \u003cp\u003e46.77 \u0026plusmn; 0.29\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e66.79 \u0026plusmn; 1.61\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003eVA only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e43.50 \u0026plusmn; 1.50\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19%;\"\u003e\n \u003cp\u003e46.75 \u0026plusmn; 0.11\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e64.17 \u0026plusmn; 2.28\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003ePretreatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e44.00 \u0026plusmn; 1.00\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19%;\"\u003e\n \u003cp\u003e44.93 \u0026plusmn; 0.68\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e61.09 \u0026plusmn; 4.09\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003ePretreatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e45.50 \u0026plusmn; 0.50\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19%;\"\u003e\n \u003cp\u003e46.54 \u0026plusmn; 0.11\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e64.95 \u0026plusmn; 3.66\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003ePost-Treatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e43.00 \u0026plusmn; 1.00\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19%;\"\u003e\n \u003cp\u003e46.59 \u0026plusmn; 1.09\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e53.20 \u0026plusmn; 5.14\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003ePost-Treatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23%;\"\u003e\n \u003cp\u003e44.50 \u0026plusmn; 0.50\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19%;\"\u003e\n \u003cp\u003e47.86 \u0026plusmn; 0.44\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18%;\"\u003e\n \u003cp\u003e61.35 \u0026plusmn; 3.01\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eValues are stated as Mean\u0026nbsp;\u003c/em\u003e\u003cimg width=\"10\" height=\"18\" src=\"https://myfiles.space/user_files/58895_8739fc6c57c1c19a/58895_custom_files/img176293118542.png\" alt=\"image\"\u003e\u003cem\u003e\u0026nbsp;SEM (n=5)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFor each parameter, values having different superscripts between groups differ significantly (p\u0026lt;0.05).\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffect of ethanol extract of \u003cem\u003eV. amygdalina\u003c/em\u003e on concentrations of malondialdehyde and nitric oxide in cardiac tissues\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;of rats\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, there were significant increase (\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) in the mean values of cardiac NO and MDA in the DMH group when compared with control and the other groups as shown in Table 9. Consequently, treatment of rats with ethanol extract of \u003cem\u003eV. amygdalina\u003c/em\u003e significantly decreased (\u003cem\u003ep\u0026lt;\u003c/em\u003e0.05) these values close to normal levels (Table 9)\u003cstrong\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 9: Levels of Malondialdehyde and Nitric Oxide in Cardiac Tissues\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"570\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.4737%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMDA\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(mole/mg tissue) x 10\u003csup\u003e-3\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.5263%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNitric Oxide (\u0026micro;mol/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.4737%;\"\u003e\n \u003cp\u003e2.50 \u0026plusmn; 0.50\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.5263%;\"\u003e\n \u003cp\u003e36.95 \u0026plusmn; 12.55\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003eDMH\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.4737%;\"\u003e\n \u003cp\u003e14.50 \u0026plusmn; 1.50\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.5263%;\"\u003e\n \u003cp\u003e59.95 \u0026plusmn; 2.05\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003eSilymarin\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.4737%;\"\u003e\n \u003cp\u003e3.50 \u0026plusmn; 0.50\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.5263%;\"\u003e\n \u003cp\u003e30.10 \u0026plusmn; 5.40a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003eVA only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.4737%;\"\u003e\n \u003cp\u003e2.67 \u0026plusmn; 0.33\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.5263%;\"\u003e\n \u003cp\u003e41.80 \u0026plusmn; 0.60\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003ePretreatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.4737%;\"\u003e\n \u003cp\u003e5.00 \u0026plusmn; 1.00\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.5263%;\"\u003e\n \u003cp\u003e40.55 \u0026plusmn; 18.25\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003ePretreatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.4737%;\"\u003e\n \u003cp\u003e3.67 \u0026plusmn; 0.33\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.5263%;\"\u003e\n \u003cp\u003e40.25 \u0026plusmn; 3.35\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003ePost-Treatment (200 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.4737%;\"\u003e\n \u003cp\u003e5.00 \u0026plusmn; 1.00\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.5263%;\"\u003e\n \u003cp\u003e41.50 \u0026plusmn; 0.80\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40%;\"\u003e\n \u003cp\u003ePost-Treatment (400 mg/kg bwt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29.4737%;\"\u003e\n \u003cp\u003e4.00 \u0026plusmn; 1.00\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30.5263%;\"\u003e\n \u003cp\u003e40.85 \u0026plusmn; 1.85\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eValues are stated as Mean\u0026nbsp;\u003c/em\u003e\u003cimg width=\"10\" height=\"18\" src=\"https://myfiles.space/user_files/58895_8739fc6c57c1c19a/58895_custom_files/img176293118416.png\" alt=\"image\"\u003e\u003cem\u003e\u0026nbsp;SEM (n=5)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFor each parameter, values having different superscripts between groups differ significantly (p\u0026lt;0.05).\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHeart\u003c/strong\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this current research, the rats were exposed to 1, 2 dimethylhydrazine (DMH) before and after \u003cem\u003eVernonia amygdalina\u003c/em\u003e administration. Results obtained for the body weight of rats as shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e, indicated that the DMH group recorded significant reductions (\u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05) in the final body weight when compared with control and the other groups. However, there was a significant increase (\u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05) in the relative weight of the heart when compared with other groups as shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e3\u003c/span\u003e. When rats are exposed to toxicants, they typically experience a decrease in body weight when compared to normal rats, meaning the exposure to DMH can lead to weight loss in the animals; this is often used as an indicator of toxicity and is frequently studied in research investigating potential preventive treatments for diseases [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The percentage increases in body weight of rats treated with ethanol extract of \u003cem\u003eV. amygdalina\u003c/em\u003e leaves were significantly increased (\u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05), relative to the DMH group as shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e2\u003c/span\u003e. This implies that the extract possesses beneficial properties for weight management. This agrees with a similar study carried out by [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDyslipidemia is a condition of abnormal lipids, such as high triacylglycerol, cholesterol, and low-density lipoprotein cholesterol levels, which is characterized by metabolic disorders highly associated with obesity [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Lipid profile in plasma and tissues are important diagnostic tools, particularly in conditions such as obesity, diabetes mellitus, coronary heart disease, atherosclerosis, hypertension, infertility, obstructive jaundice, hepatitis and other diseases characterized by abnormalities of lipid metabolism [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Results obtained from the lipid profile of rats in the DMH group as shown in Table \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Table \u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e5\u003c/span\u003e, recorded a high significant increase (\u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05) in the plasma levels of total cholesterol (TC), triglyceride (TG), very low-density lipoprotein-cholesterol (VLDL-C) and low-density lipoprotein-cholesterol (LDL-C), while high density lipoprotein-cholesterol (HDL-C) was significantly reduced relative to control and the other groups. This implies that DMH administration can lead to dyslipidemia which is a known condition of abnormal lipids in the body [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Consequently, the pre- and post-treatment groups revealed significant decreases (\u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05) in plasma levels of TC, TG, LDL-C and VLDL-C, and an increase (\u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05) in HDL-C levels when compared to the DMH groups. These observed effects of \u003cem\u003eV. amygdalina\u003c/em\u003e in the plasma levels of lipid profile in DMH rats suggest that the extract is effective in ameliorating complications such as cardiovascular disease, arteriosclerosis, coronary artery disease etc. owing to its high content of polyphenols which are bioactive components in the extract [26, 27]. The elevated levels (\u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05) of the cardiovascular disease risk factors [atherogenic index of plasma (AIP), atherogenic coefficient (AC) and cardiac risk ratio (CRR)], in the DMH group as shown in Table \u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e6\u003c/span\u003e, implies that there might be an increased risk of coronary heart disease and arteriosclerosis [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. On the other hand, these changes were significantly reverted (\u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05) especially in the pre- and post-treatment groups relative to the control, silymarin and DMH groups respectively. This implies that \u003cem\u003eV. amygdalina\u003c/em\u003e can reduce complications of cardiovascular disease such as blood pressure in rats, further contributing to its cardiovascular benefits [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAntioxidant enzymes are crucial for protecting the body against the damaging effects of reactive oxygen species (ROS) or free radicals. They neutralize these highly reactive molecules, preventing them from causing harm to cells and tissues. By reducing ROS, antioxidant enzymes help maintain a healthy balance in the body, supporting overall well-being [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Exposure of Wistar albino rats to DMH led to significant reductions (\u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05) in the concentrations of cardiac antioxidant enzymes (CAT, SOD, GPx, GSH, GR and % GSH) relative to control and the other groups as shown in Table \u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e7\u003c/span\u003e and Table \u003cspan refid=\"Tab9\" class=\"InternalRef\"\u003e8\u003c/span\u003e. The decrease observed in these parameters occurred due to the formation of free radicals caused by oxidative stress thereby leading to decrease in membrane fluidity, cell injury and cell death [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. However, treatment of rats before and after DMH administration with ethanol extract of \u003cem\u003eV. amygdalina\u003c/em\u003e significantly increased (\u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05) the levels of the antioxidant enzymes when compared with the DMH group. This suggests that the extract relieves heart tissues from inflammation and minimizes oxidative stress and cell injury [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Other studies further shows that the extract contains vitamins and trace elements that promote healing in heart tissue [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn cardiac tissues, elevated levels of both malondialdehyde (MDA) and nitric oxide (NO) can be indicators of oxidative stress and potential heart damage. MDA, a product of lipid peroxidation, reflects oxidative stress, while NO, a vasodilator, can be affected by oxidative stress in the heart [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. In this study, there were significant increase (\u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05) in the mean values of cardiac NO and MDA in the DMH group when compared with control and the other groups as shown in Table \u003cspan refid=\"Tab10\" class=\"InternalRef\"\u003e9\u003c/span\u003e. The remarkable elevations of these parameters suggests that there is an increase in lipid peroxidation, loss of vascular integrity, coronary artery disease, atherosclerosis, blood pressure and smooth muscle cell proliferation [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Consequently, treatment of rats with ethanol extract of \u003cem\u003eV. amygdalina\u003c/em\u003e significantly decreased (\u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05) these values close to normal levels which means that the extract may have protective effects against oxidative stress and inflammation in the heart [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the histology studies, sections of heart tissues in rats exposed to DMH alone showed severe congestion of blood vessels and derangement of muscle fiber when compared with control and other groups (Plate 1 and Plate 2). Sections of cardiac tissues of rats that received only \u003cem\u003eV. amygdalina\u003c/em\u003e and silymarin revealed normal myocytes, coronary artery and mild congestion with peripherally placed nuclei surrounded by normal eosinophilic cytoplasm (Plate 3 and Plate 4). Segments of cardiac muscles of the pre- and post-treatment groups at lower and higher doses revealed moderate myocytes, mild vascular architecture and mild vascular dilation with peripherally placed nuclei surrounded by eosinophilic cytoplasm which is consistent with the control group (Plate 5, Plate 6, Plate 7 and Plate 8). The defects in heart tissue histoarchitecture seen in the DMH group is due to edema, vasoconstriction, severe glassy or waxy hyaline degeneration, and necrosis of skeletal muscles [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. \u003cem\u003eV. amygdalina\u003c/em\u003e treatment prior to or after DMH induction at lower and higher doses suggests that the extract might have cardioprotective effects in rats, potentially by reducing oxidative stress and apoptosis, and improving heart histology [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. This shows that the extract enhances the antioxidant defense system in rats, potentially reducing oxidative stress-induced damage in heart histology [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe results of this study have shown that \u003cem\u003eVernonia amygladina\u003c/em\u003e is able to suppress or reduce oxidative stress associated with cardiac toxicity in rats due to phytochemicals such as saponins and polyphenols present in the plant extract. Thus, further research on \u003cem\u003eVernonia amygladina\u003c/em\u003e may reveal its potential as a source of phyto-medicine which can be presented as a recommendation for clinical trials.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e%GSH \u0026ndash; Concentration of Reduced Glutathione\u003c/p\u003e\n\u003cp\u003eAC \u0026ndash; Atherogenic coefficient\u003c/p\u003e\n\u003cp\u003eAIP \u0026ndash; Atherogenic index of plasmas\u003c/p\u003e\n\u003cp\u003eANOVA \u0026ndash; Analysis of variance\u003c/p\u003e\n\u003cp\u003eAOM \u0026ndash; Azoxymethane (AOM) \u003c/p\u003e\n\u003cp\u003eCRR \u0026ndash; Cardiac risk ratio \u003c/p\u003e\n\u003cp\u003eCVD \u0026ndash; Cardiovascular disease\u003c/p\u003e\n\u003cp\u003eDMH \u0026ndash; 1, 2- Dimethyl hydrazine\u003c/p\u003e\n\u003cp\u003eDNA \u0026ndash; Deoxyribonucleic Acid\u003c/p\u003e\n\u003cp\u003eEDTA \u0026ndash; Ethylenediaminetetraacetic acid \u003c/p\u003e\n\u003cp\u003eGPx \u0026ndash; Glutathione Peroxidase\u003c/p\u003e\n\u003cp\u003eGR \u0026ndash; Glutathione reductase\u003c/p\u003e\n\u003cp\u003eGSH \u0026ndash; Glutathione \u003c/p\u003e\n\u003cp\u003eHDL-C \u0026ndash; High Density Lipoprotein Cholesterol\u003c/p\u003e\n\u003cp\u003eLDL-C \u0026ndash; Low Density Lipoprotein Cholesterol\u003c/p\u003e\n\u003cp\u003eMDA \u0026ndash; Malondialdehyde\u003c/p\u003e\n\u003cp\u003eROS \u0026ndash; Reactive Oxygen Species\u003c/p\u003e\n\u003cp\u003eSEM \u0026ndash; Standard Error Mean\u003c/p\u003e\n\u003cp\u003eSOD \u0026ndash; Superoxide Dismutase\u003c/p\u003e\n\u003cp\u003eTAG \u0026ndash; Triacylglycerol\u003c/p\u003e\n\u003cp\u003eTP \u0026ndash; Total Protein\u003c/p\u003e\n\u003cp\u003eUBTH \u0026ndash; University of Benin Teaching Hospital\u003c/p\u003e\n\u003cp\u003eVA \u0026ndash; \u003cem\u003eVernonia amygdalina\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eVLDL \u0026ndash; Very Low-Density Lipoprotein\u003c/p\u003e\n\u003cp\u003eWHO \u0026ndash; World Health Organization\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe experimental protocol for this study was approved by the Faculty of Life Science Ethical Committee of University of Benin, Benin City, Edo State, Nigeria.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article [and its supplementary information files].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAOO conceived the idea for the work, Methodology, AOO and ODA designed the study, AO and ODA were involved in carrying out the analysis and interpretation of data generated in this study, AO and ODA provided resources such as assay kits and laboratory equipment for this study, AOO prepared the original draft/manuscript of this work, ODA substantively reviewed and edited the work, ODA approved the submitted version of the work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSishi BJN. 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The role of superoxide anion in the autooxidation of epinephrine and- a simple assay for superoxide dismutase. J Biol Chem. 1972; 247:3170\u0026ndash;5. https://doi.org/10.1016/S0021-9258(19)45228-9\u003c/li\u003e\n\u003cli\u003eGoth L. A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta. 1991;196(2\u0026ndash;3):143\u0026ndash;51. https://doi.org/10.1016/0009-8981(91)90067-M\u003c/li\u003e\n\u003cli\u003eEllman GL. \u0026ldquo;Tissue sulfhydryl groups,\u0026rdquo; Archives of Biochemistry and Biophysics, 1959; 82(1):70\u0026ndash;77. https://doi.org/10.1016/0003-9861(59)90090-6\u003c/li\u003e\n\u003cli\u003eUmeaku U, David A, Ofusori Obioma, PU, Tolulope AE. The Effect of Aqueous Extract of Ocimum gratissium (Linn) on 1, 2 - Dimethyl Hydrazine induced Colon Cancer in Male Wistar Rats. International Journal of Human Anatomy, 2020;2:(1):22-35. DOI:10.11648/j.fem.20190501.13\u003c/li\u003e\n\u003cli\u003eObike CA, Ijeh II, Egbuonu ACC, Ubah EE. Body and Organ Weight Changes in Male Wistar Rats Treated with Saponins Extract of Vernonia amygdalina and Vernonia colorata. Scientia Africana, 2024;23,(3):133-146. DOI: 10.4314/sa.v23i3.13\u003c/li\u003e\n\u003cli\u003eAdeyemi OS, Orekoya BT. Lipid Profile and Oxidative Stress Markers in Wistar Rats following Oral and Repeated Exposure to Fijk Herbal Mixture. J Toxicol. 2014; 2014:876035. doi: 10.1155/2014/876035. \u003c/li\u003e\n\u003cli\u003eOlooto WE, Ogunkoya OO, Alabi AO, Oyinloye OE. Hypolipidaemic Potentials of Vernonia amygdalina (Bitter Leaf) in male albino rats fed high-sucrose diet. Annals of Health Research, 2017;3(1):10-17. http://orcid.org/0000-0003-4723-8131\u003c/li\u003e\n\u003cli\u003eChithra V, Leelamma S. Coriandrum sativum--effect on lipid metabolism in 1,2-dimethylhydrazine induced colon cancer. J Ethnopharmacol. 2000;71(3):457-63. doi:10.1016/s0378-8741(00)00182-3. \u003c/li\u003e\n\u003cli\u003eAdaramoye OA, Akintayo O, Achem J, Fafunso MA. Lipid-lowering effects of methanolic extract of Vernonia amygdalina leaves in rats fed on high cholesterol diet. Vasc Health Risk Manag. 2008;4(1):235-41. doi: 10.2147/vhrm.2008.04.01.235.\u003c/li\u003e\n\u003cli\u003eAbdulmalik O, Oladapo OO, Bolaji MO. Effect of aqueous extract of Vernonia amygdalina on atherosclerosis in rabbits. ARYA Atheroscler. 2016;12(1):35-40. \u003cbr\u003e DOI:10.1007/978-3-031-43199-9_75\u003c/li\u003e\n\u003cli\u003eEdo GI, Samuel PO, Jikah AN, Onoharigho FO, Idu LI, Obasohan P, et al. Biological and bioactive components of bitter leaf (Vernonia amygdalina leaf): Insight on health and nutritional benefits. A review, Food Chemistry Advances, 2023;3:100488, https://doi.org/10.1016/j.focha.2023.100488.\u003c/li\u003e\n\u003cli\u003eUchendu IK, Ikebunwa OA, Okpagu CB. Cardiorenal protective effects of extracts of bitter leaf (Vernonia amygdalina L.) in animal model of metabolic syndrome. Foods and Raw Materials. 2024;12(2):264\u0026ndash;272. https://doi.org/10.21603/2308-4057-2024-2-607 \u003c/li\u003e\n\u003cli\u003eOmisore AD, Abiodun AA, Adeyemi DO, Abijo AZ, Jolayemi KA, Odedeyi AA. Therapeutic effects of \u003cem\u003eVernonia amygdalina\u003c/em\u003e on the expression of hormone and HER2 receptors in 7, 1, 2-dimethylbenz(a)anthracene-induced breast tumours in obese and non-obese Wistar rats, Phytomedicine Plus, 2022;2(3):100318, https://doi.org/10.1016/j.phyplu.2022.100318.\u003c/li\u003e\n\u003cli\u003eRadovanovic J, Banjac K, Obradovic M, Isenovic ER. Antioxidant enzymes and vascular diseases. Explor Med. 2021; 2:544\u0026ndash;55. https://doi.org/10.37349/emed.2021.00070\u003c/li\u003e\n\u003cli\u003eTseng TH, Hsu JD, Chu CY, Wang CJ. Promotion of colon carcinogenesis through increasing lipid peroxidation induced in rats by a high cholesterol diet, Cancer Letters, 1996; 100(1-2):81-87 https://doi.org/10.1016/0304-3835(95)04073-0.\u003c/li\u003e\n\u003cli\u003eCh\u0026apos;ng YS, Loh YC, Tan CS, Ahmad M, Asmawi MZ, Wan Omar WM, Yam MF. Vasorelaxant properties of Vernonia amygdalina ethanol extract and its possible mechanism. Pharm Biol. 2017;55(1):2083-2094. doi: 10.1080/13880209.2017.1357735.\u003c/li\u003e\n\u003cli\u003eNguemfo TA, Mbida M, Hescheler J, Nguemo F. Effect of Ethanolic Extract of Vernonia amygdalina on the Proliferation, Viability and Function of Mouse Induced Pluripotent Stem Cells and Cardiomyocytes. Plants. 2023; 12(5):1108. https://doi.org/10.3390/plants12051108\u003c/li\u003e\n\u003cli\u003eSerdar S, Ahmet \u0026Ccedil;, Seniz D, Vedat D, Mehmet T, Mehmet A. The relationship between oxidative stress, nitric oxide, and coronary artery disease. European Journal of General Medicine, 2007;4(2):62-66. https://doi.org/10.5683/SP3/WU14SM.\u003c/li\u003e\n\u003cli\u003eKelm M, Feelish M, Deussen A, Strauer BE, Schrader J. Release of endothelium derived nitric oxide in relation to pressure and flow. Cardiovascular Research. 1991; 25:831\u0026ndash;836 DOI: 10.1093/cvr/25.10.831\u003c/li\u003e\n\u003cli\u003eErukainure OL, Oyebode OA, Ibeji CU. Koorbanally NA, Islam MS. Vernonia Amygdalina Del. stimulated glucose uptake in brain tissues enhances antioxidative activities; and modulates functional chemistry and dysregulated metabolic pathways. Metabolic Brain Disorder, 2019;34:721\u0026ndash;732 DOI: 10.1007/s11011-018-0363-7\u003c/li\u003e\n\u003cli\u003eAl-Hamdany EK, Al-Mallah KH, Ismail HK. Histopathological evaluation of lesions induced by dimethyl hydrazine in male rats. Iraqi Journal of Veterinary Sciences, 2022; 36(Supplement I): 115-121. doi: 10.33899/ijvs.2022.135760.2515\u003c/li\u003e\n\u003cli\u003ePrananda AT, Dalimunthe A, Harahap U, Abdi SR, Nugraha SE, Situmorang PC, Fah YT, Velaro AJ, Bilakaya B, Harahap M. Vernonia amygdalina protects against doxorubicin-induced hepatic and renal damage in rats: mechanistic insights. Pharmacia 2023;\u003cstrong\u003e70\u003c/strong\u003e(3): 825-835. DOI 10.3897/pharmacia.70.e112425\u003c/li\u003e\n\u003cli\u003eUgwoke C, Nzekwe U, Ameh G. Phytochemical constituents and ethnobotany of the leaf extract of bitter leaf (Vernonia amygdalina Del.) Journal of Pharmaceutical and Allied Sciences, 2011;7(3). https://doi.org/10.4314/jophas.v7i3.63409\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Plate","content":"\u003cp\u003ePlates 3.1 to 3.8 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"Toxicity, Vernonia amygdalina, intraperitoneal, ethanol extract, lipid, cardiovascular, systemic, antioxidant","lastPublishedDoi":"10.21203/rs.3.rs-8029156/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8029156/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCardiotoxicity is an emerging condition that occurs due to systemic toxicity resulting from 1,2 dimethylhydrazine (DMH) exposure. Until now, nothing is known about the role of \u003cem\u003eVernonia amygdalina\u003c/em\u003e in suppressing lipid abnormalities and oxidative stress caused by DMH cardiotoxicity in rats. Our novel treatment measures tend to be beneficial in combating heart toxicity resulting from DMH exposure. This study was conducted to investigate the cardioprotective potentials of \u003cem\u003eVernonia amygdalina\u003c/em\u003e on 1,2-Dimethylhydrazine induced toxicity in rats\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAdult male Wistar rats were exposed to 1, 2 dimethylhydrazine (DMH) toxicity via the intraperitoneal route at a single dose of 40 mg/kg body weight before and after treatment with lower (200 mg/kg body weight) and higher (400 mg/kg body weight) doses of \u003cem\u003eVernonia amygdalina\u003c/em\u003e ethanol extract. Lipid profile parameters, cardiovascular disease risks factors and oxidative stress markers were measured in plasma and heart tissue homogenates of rats using standardized protocols, while portions of the excised heart specimens were subjected to histopathological examination. Data analysis and post-hoc test for this study were performed using SPSS version 20.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe concentrations of heart tissue antioxidant enzymes (CAT, SOD, GPx, GSH, GR and GSH (%)) in the DMH group were significantly reduced (p\u0026lt;0.05) relative to control and the other groups. However, administration of ethanol extract of \u003cem\u003eV. amygdalina\u003c/em\u003e to rats significantly increased (p\u0026lt;0.05) these levels when compared with the DMH group. Furthermore, there was a significant decrease (p\u0026lt;0.05) in the mean values of cardiovascular disease risk factors, cardiac Nitric Oxide (NO), and Malondialdehyde (MDA) in the treatment groups when compared with control and DMH group. Heart tissues of DMH-induced rats treated with \u003cem\u003eVernonia amygdalina\u003c/em\u003e revealed a significant reduction (p\u0026lt;0.05) in organ weight relative to the control group. Histological studies revealed the protective and regenerative effects of \u003cem\u003eVernonia amygdalina\u003c/em\u003e on heart tissues.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe findings from this study indicates that \u003cem\u003eVernonia amygdalina\u003c/em\u003e can effectively suppress irregularities in the lipid profile, cardiovascular disease risk factors, and oxidative stress parameters caused by DMH toxicity due to its antioxidant properties. This impliesthat \u003cem\u003eVernonia amygdalina\u003c/em\u003e holds promise as a novel therapeutic strategy for improving DMH systemic toxicity.\u003c/p\u003e","manuscriptTitle":"Cardioprotective Potentials of Vernonia amygdalina on 1,2-Dimethylhydrazine Induced Toxicity in Rats","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-12 07:22:41","doi":"10.21203/rs.3.rs-8029156/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":"e1aed7bf-e68c-4c2a-8be8-59f92ced8f2d","owner":[],"postedDate":"November 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-27T13:23:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-12 07:22:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8029156","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8029156","identity":"rs-8029156","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}