Telfairia occidentalis seed extract and fractions mitigated doxorubicin-induced cardiotoxicity in rats

 Corresponding author: Jude E. Okokon Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution License 4.0. Telfairia occidentalis seed extract and fractions mitigated doxorubicin-induced cardiotoxicity in rats Ugochi Q. Nwosu 1, Kenneth Chidi Opara 2, Chinyelu C. Osigwe 3, Ugonma F. Uwaeme 3, Unyime A. Fabian 4 and Jude E. Okokon 1, * 1 Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Uyo, Uyo, Nigeria. 2 Department of Family Medicine, Federal Teaching Hospital, Owerri, Imo State, Nigeria. 3 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Madonna University Nigeria, Elele campus, Rivers State, Nigeria. 4 Faculty of Allied Health sciences, Department of Medical Laboratory Sciences University of Uyo, Uyo, Nigeria. GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 019-030 Publication history: Received on 21 August 2025; revised on 01 October 2025; accepted on 03 October 2025 Article DOI: https://doi.org/10.30574/gscbps.2025.33.1.0375 Abstract Telfaira occidentalis Hook (Cucurbitaceae) seeds are used in the preparation of soups and as medicine traditionally to treat various diseases. This study was designed to investigate the antidotal potentials of the crude extract and fractions of Telfairia occidentalis seed against doxorubicin-induced heart toxicity in rats. The seed extract (138-553 mg/kg) and fractions (dichloromethane and aqueous, 276 mg/kg) of the plant were investigated for antioxidative stress and cardioprotective potentials against doxorubicin-induced heart toxicity in rat. Effect of the seed extract and fractions on cardiac marker enzymes, oxidative stress markers, lipid profile indices and heart histology were used as parameters to assess the cardioprotective effect of the extract and fractions. The seed extract and fractions (138-553 mg/kg) significantly (p<0.05-0.01) reduced the serum levels of CK-MB, LDH and troponin I that were elevated by doxorubincin. Also, the levels of GSH, SOD, GPx and CAT in the heart that were decreased by doxorubicin were significantly (p<0.01) elevated and the raised MDA level was reduced by the seed extract and fractions. The seed extract and fractions also reduced significantly (p<0.05) the serum levels of total cholesterol, triglycerides, LDL and VLDL of the treated rats elevated by doxorubicin. Histology sections of hearts of extract/fractions -treated animals showed reductions in the pathological features compared to the organotoxic-treated animals. The chemical pathological changes were consistent with histopathological observations suggesting marked cardioprotective potentials. The anti-toxic effect of this plant may in part be mediated through the chemical constituents of the plant. The seed extract of Telfairia occidentalis possesses anti-toxicant properties which can be exploited in the treatment of poisoning. Keywords: Telfairia occidentalis; Anti-Toxicant; Oxidative Stress; Cardioprotective; Antioxidant 1. Introduction Drug-induced cardiotoxicity is a serious clinical challenge which is associated with so many clinically useful drugs especially cytotoxic drugs one of which is doxorubicin. This often results in cardiac dysfunction and myocardial injury among others which can lead to long term morbidity even after the discontinuation of the drug [1,2]. Doxorubicin (DOX)- induced cardiotoxicity has been suggested to results from free radicals’ generation and lipid peroxidation in myocardial cells [3,4]. These undesirable organs toxicities associated with doxorubicin have limited its clinical usefulness and therefore necessitate extensive research into agents that can prevent and or ameliorates these toxic effects. GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 019-030 20 Telfairia occidentalis Hook is a fluted pumpkin of the Cucurbitaceae family widely consumed as food in Nigeria [5]. It is a popular vegetable all over Nigeria, especially in the Niger-Delta region and the Eastern part of the country; varieties of meals are prepared from the leaves, stem and seeds of the plant [6]. The seeds are very nutritious and are eaten roasted or boiled. The seed has history of being effective in the treatment and prevention of prostrate disorders. The seed extract has been reported to exert antidiabetic [7], cellular antioxidant, immunodulatory, anticancer, antiinflammatory [8], antiplasmodial [5], antioxidant and analgesic [9,10], genotoxic and cytotoxic [11] and in vivo inhibitory effect alpha amylase and alpha glucosidase [12]. while the leaf extract possesses antioxidant, antibacterial [13], hepatoprotective [14] antidiabetic [15], antiplasmodial [5] genotoxic and cytotoxic [11] and antiprostatic [16] activities. Phytochemical studies of the seed extract have shown the presence of alkaloid, flavonoid, tannins, terpenes, saponin, and cardiac glycosides [17]. Okokon et al. [8] reported the presence of compounds such as pentadecanoic acid, hexadecanoic acid; 16-octadecenoic acid methyl ester; 9, 12-octadecadienoyl chloride (Z,Z); 9octadecadienoic acid (Z)- , 2, 3-dihydroxypropyl ester; octadecanoic acid; hexadecanoic acid,2,3-is[(trimethylsilyl) oxy] propyl ester, 2,4heptadien-6-ynal,(E,E); benzoic acid ; dodecanoic acid ; linoleic acid ethyl ester ; hexadecanoic acid, methyl ester ; αphellandrene; α-campholene aldehyde; terpinen-4-ol; trans-β-ocimene; borneol and stigmastan-3ol, in the seed extract. The present study was designed to evaluate the activities of seed extract and fractions of T. occidentalis against doxorubicin-induced cardiotoxicity in rats. 2. Materials and Methods 2.1. Plant collection and extraction Fresh seeds of Telfairia occidentalis were purchased from Itam market in Itu L. G. A, Akwa Ibom State, Nigeria, in June, 2023. The seeds were previously identified and authenticated by a taxonomist in the Department of Botany, University of Uyo, Uyo, Nigeria. Herbarium specimens (UUPH 1(b)) were deposited at Department of Pharmacognosy and Natural Medicine Herbarium, University of Uyo. The fresh seeds of the plant were dried on laboratory table for 2 weeks and reduced to powder. The seeds powder (1 kg) was macerated in 50% ethanol (5000 mL) for 72 hours. The liquid filtrates obtained were concentrated at 40˚C and all the ethanol was completely removed. The crude extract (20 g) was dissolved in 500 mL of distilled water and partitioned with equal volume of dichloromethane (DCM, 5 x 500 mL) till no colour change was observed, to obtain DCM and aqueous fractions. The extract and fractions were stored at 4˚C in a refrigerator until used for the experiment. 2.2. Animals In this study, male albino Wistar rats (150-200 g) were used. The animals were sourced from University of Uyo Animal house and sheltered in plastic cages. The rats were fed with pelleted standard Feed (Guinea feed) and given unlimited access to water. The study was approved by College of Health Sciences Animal Ethics Committee, University of Uyo. 2.3. Experimental design In this study, repeated dose model earlier described by Olorundare et al. [18], which lasted for 14 days was used. Groups I rats which served as the untreated control were orally pretreated with 10 mL/kg/day of distilled water. Group 2 rats were given normal saline (10 mL/kg/day) but equally treated intraperitoneally with 1.66 mg/kg of doxorubicin hydrochloride dissolved in 0.9% normal saline on alternate days for 14 days. Groups 3-5 rats were orally pretreated respectively with 138 mg/kg/day, 276 mg/kg/day, and 553 mg/kg/day of Telfairia occidentalis seed extract dissolved in 10% Tween 80, 2 hours before treatment with 1.66 mg/kg of doxorubicin dissolved in 0.9% normal saline administered intraperitoneally on alternate days for 14 days. Groups 6 and 7 were pretreated with 276 mg/kg of DCM and aqueous fractions respectively but administered with 1.66 mg/kg of doxorubicin dissolved in 0.9% normal saline administered intraperitoneally on alternate days for 14 days Group 8 rats which served as the positive control group were equally pretreated with 100 mg/kg/day of silymarin two hours before treatment with 1.66 mg/kg of doxorubicin in 0.9% normal saline administered intraperitoneally on alternate days for 14 days. 2.4. Collection of blood samples and organs After 14 days of treatment (24 hours after the last administration), the rats were weighed again and sacrificed under light diethyl ether vapour. Blood samples were collected into plain centrifuge tubes and allowed to stand for two hour before being centrifuged at 1500 rpm for 15 mins to separate the serum at room temperature and used for biochemical assays. The hearts of the rats were surgically removed, weighed. Each heart was gently and carefully divided into two GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 019-030 21 parts; a part was fixed in 10 % formaldehyde for histological processes, while the other part of the heart was briskly rinsed in ice cold 1.15% KCl solution and put in a clean sample bottle. These were stored in ice cold 0.9% NaCl. 2.5. Biochemical Assays The stored sera samples collected from the rats used in this study were used for the biochemical assays. The clear samples were obtained for assays of the following biochemical parameters: serum cardiac troponin I, lactate dehydrogenase (LDH), and creatine phosphokinase (CK-MB). 2.5.1. Measurement of Cardiac marker Enzymes. Cardiac enzymes (Creatine phosphokinase –MB (CK-MB), lactic acid dehydrogenase (LDH), and troponin I were measured by using the ELISA kit. All the tests were performed according to the manufacturer’s instruction. LDH (LDH kit-Aspen Laboratories Pvt. Ltd., Baddi; India.), Troponin I and CK-MB (Teco Diagnostics, Anaheim, USA). 2.5.2. Assessment of effect of seed extract on lipid profile The stored sera samples collected from the rats used in this study were used to determine the lipid profile parameters such as serum cholesterol, triglyceride and high-density lipoprotein (HDL) levels of the treated rats using standard colorimetric methods [19]. These lipid parameters determinations were done spectrophotometrically using Fortress Diagnostic Kits® according to standard procedures of manufacturer’s protocols. Low and very low-density lipoprotein (LDL and VLDL) were estimated from the formula of Friedwald et al. [20]. 2.5.3. Effect of the seed extract on heart oxidative stress markers The parts of heart samples stored in ice cold normal saline were used in preparation of homogenates for assay of oxidative stress markers. Homogenates were made in a ratio of 1 g of wet tissue to 9 mL of 1.25% KCl by using motor driven Teflon-pestle. The homogenates were centrifuged at 7000 rpm for 10 min at 4˚C and the supernatants were used for the assays of superoxide dismutase (SOD) [21] , catalase (CAT) [22], glutathione peroxidase (GPx) [23], reduced gluthathione (GSH) [24] and malondialdehyde (MDA) content [25]. These oxidative stress markers were used to assess antioxidative stress potentials of the extract. 2.5.4. Histopathological studies The hearts’ parts fixed in 10 % buffered formalin were used for histological processes. They were processed and stained with haematotoxylin and eosin (H&E) [26], according to standard procedures at Department of Chemical Pathology, University of Uyo Teaching Hospital, Uyo. Morphological changes were observed and recorded in the excised organs of the sacrificed animals. Histologic pictures were taken as micrographs. 2.6. Statistical analysis Data collected were analyzed using one way analysis of variance (ANOVA) followed by Tukey Krammer’s multiple comparison post-test (Graph pad prism software Inc. La Jolla, CA, USA). Values were expressed as mean ± SEM and significance relative to control were considered at p˂0.001 and p˂0.05. 3. Results 3.1. Effect of seed extract and fractions of T. occidentalis on body and organs weights of rats with doxorubicininduced toxicity Administration of T. occidentalis seed extract and fractions to rats with doxorubicin-induced organs toxicities caused considerable improvement of the body weights compared to the organotoxic group. The crude extract (276 mg/kg) and dichloromethane fraction treated groups recorded the highest body weight gains compared to the organotoxic group. However, these were non-dose-dependent and insignificant when compared to the organotoxic group. The heart weights of the group treated with doxorubicin only were found to be increased when compared to those of the normal control group though not statistically significant (p>0.05). However, concommitant treatment of rats with doxorubicin and seed extract and fractions of T. occidentalis improved the organs weights though insignificantly (p>0.05) relative to the group treated with doxorubicin only (Table 1). GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 019-030 22 3.2. Evaluation of effect of seed extract and fractions of T. occidentalis on cardiac marker enzymes of doxorubicin-induced heart injuries in rats: The effect of seed extract and fractions of T.occidentalis on cardiac marker enzymes of normal rats and rats with doxorubicin-induced toxicities is as presented in Table. Treatment of rats with doxorubicin (1.66 mg/kg i.p) on alternate days for 14 days caused significant (p<0.01-0.001) elevation of cardiac marker enzymes (troponin I, lactate dehydrogenase and CK-MB) activities when compared to normal control. The increases in the levels of lactate dehydrogenase, troponin I and CK-MB were dose-dependently and significantly (p< 0.05-0.001) reduced when compared to organotoxic group following concomitant treatment of the rats with seed extract and fractions of T.occidentalis (138-553 mg/kg) with the highest dose of the extract (553 mg/kg) and aqueous fraction having the highest effect. Similar effect was observed in the group treated with silymarin. (Figures 1, 2 and 3). 3.3. Effect of T. occidentalis seed extract and fraction on heart oxidative stress markers of doxorubicin-induced heart toxicity Table 2 shows the effect of T. occidentalis seed extract/fractions on oxidative stress markers of the heart. Administration of doxorubicin (1.66 mg/kg i.p) on alternate days for 14 days caused decreases of cardiac antioxidant enzymes activities (SOD, GPx, GST, CAT) and GSH levels which were significant (p<0.05-0.001) when compared to control except in CAT level. The MDA level was also significantly (p<0.01) elevated by doxorubicin treatment relative to control. However, concomitant administration of seed extract/fractions of T.occidentalis (138553 mg/kg) with doxorubicin for 14 days caused marked elevations of the enzymatic and non-enzymatic endogenous antioxidants in the treated rats’ groups when compared to the organotoxic groups. The elevations in the levels of SOD and CAT were dose-dependent and significant (0.05-0.01) in the groups treated with the highest dose (553 mg/kg). DCM fraction treated group had the most significant (p<0.001) elevation of SOD, while CAT level was significantly (p<0.001) raised by aqueous fraction when compared to control. GPx and GSH levels were also dose-dependently elevated with DCM fraction treated group having the most significant (p<0.001) effect when compared to organotoxic group. The treatment with extract/fractions also caused marked non-dose-dependent reduction in the level of MDA of the treated rats which were significant (p<0.05-0.001) in the groups treated with the low dose (138 mg/kg), aqueous fraction, DCM fraction and silymarin when compared to organotoxic control with the DCM fraction having the most significant effect (Table 2). 3.4. Effect of seed extract and fraction of T.occidentalis on lipid profile of rats with doxorubicin -induced organs toxicities Administration of doxorubicin (1.66 mg/kg) was observed to caused significant (p<0.05-0.001) elevation in levels of total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, and very low-density lipoprotein. These raised levels of total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, and very low-density lipoprotein were significantly (p<0.05-0.001) reduced when compared to organotoxic group following concommitant treatment with seed extract and fractions of T.occidentalis and silymarin. However, the reductions in total cholesterol and low-density lipoprotein were dose-dependent, while non-dose-dependent reductions were observed in triglyceride, high density lipoprotein and very low-density lipoprotein levels (Table 3). 3.4.1. Effect of seed extract and fractions of T. occidentalis on histology of rat heart in doxorubicin-induced cardiotoxicity: Histologic sections of hearts of rats receiving various treatments at magnification (x100) stained with H&E method revealed that Group 1 (normal control, CONT) treated distilled water (10 mL/kg) had cardiac section showing normal cardiac architecture with the myometrium having well-presented cardiac myocytes, myocyte nuclei, fibrocyte nuclei and endomysium and blood vessels. No pathological change was seen. The organotoxic group (Group 2, T+CONT) treated with doxorubicin (1.66 mg/kg) only revealed heart tissue showing presence of inter-muscular vascular hemorrhage and fibrosis within the cardiac myometriume. Focal hyaline degeneration was also seen. Group 3 (T+STD) treated with 100 mg/kg of silymarin of T.occidentalis seed and doxorubicin (1.66 mg/kg) had moderately affected heart tissue showing presence of inter-muscular vascular hemorrhage within the cardiac myometrium. Rats in group 4 (T+LDE) treated with 138 mg/kg of T.occidentalis seed extract and doxorubicin (1.66 mg/kg) showed moderately affected cardiac tissue revealing the presence of fibrosis within the cardiac myometrium. Group 5 (T+MDE) treated with 276 mg/kg of T. occidentalis seed extract and doxorubicin (1.66 mg/kg) showed heart tissue showing presence of inter-muscular vascular hemorrhage and fibrosis within the cardiac myometrium. Group 6 (T+HDE) treated with 553 mg/kg of T. occidentalis seed extract extract and doxorubicin (1.66 mg/kg) showed moderately affected heart tissue showing the presence of inter-muscular vascular hemorrhage and fibrosis within the cardiac myometrium. Group 7 (T+AQE) treated with 276 mg/kg of aqueous fraction of T. occidentalis seed and doxorubicin (1.66 mg/kg) showed a moderately affected heart tissue showing the presence of fibrosis within the cardiac myometrium. Rats in group 8 (T+DCME) treated with 276 mg/kg of dichloromethane fraction of T. occidentalis seed and doxorubicin (1.66 mg/kg) GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 019-030 23 moderately affected heart tissue showing the presence of inter-muscular vascular hemorrhage and fibrosis within the cardiac myometrium (Figure 4). Table 1 Effect of T. occidentalis seed extract on body and organs weights of rats with doxorubicin-induced toxicity Parameters/ Treatment Dose mg/kg Heart Body weight Before After % increase in body weight Normal control - 0.60± 0.06 176.28±17.97 198.25± 6.61 12.46 Doxorubicin 1.66 0.65± 0.01 169.66 ± 6.80 181.66±13.24 5.72 Silymarin+DOX 100 0.63±0.03 180.33± 10.86 190.66± 13.24 5.72 Extract+DOX 138 0.65±0.05 176.0± 11.13 191.0± 6.08 8.52 276 0.58±0.06 167.0± 7.57 185.0 ± 8.73 10.77 553 0.65±0.03 177.66± 7.42 193.33 ± 5.48 8.82 Aqueous fraction 276 0.69±0.10 187.66± 17.89 195.33± 17.70 4.08 DCM fraction 276 0.52±0.06 162.66± 12.66 180.33± 9.56 10.86 Data are expressed as mean ±SEM. significant at dp<0.001 when compared to normal control; ap< 0.05, bp< 0.01, cp< 0.001 when compared to organotoxic control. n = 5. Data are expressed as MEAN ± SEM, Significant at bp<0.01; cp<0.001 when compared to normal control; dp<0.05 when compared to organ toxic control; *p< 0.001 (n=5). Figure 1 Effect of T.occidentalis seed extract and fractions on Creatine phosphokinase-MB enzyme of rats with doxorubicin-induced heart toxicity GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 019-030 24 Data are expressed as MEAN ± SEM, Significant at cp<0.001 when compared to normal control; fp< 0.001, when compared to organotoxic control (n=5). Figure 2 Effect of T. occidentalis seed extract and fractions on Troponin I enzyme of rats with doxorubicin-induced heart toxicity Data are expressed as MEAN ± SEM, Significant at cp<0.001 when compared to normal control; fp< 0.001, when compared to organotoxic control (n=5). Figure 3 Effect of T.occidentalis seed extract and fractions on lactate dehydrogenase enzyme of rats with doxorubicin-induced heart toxicity GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 019-030 25 Table 2 Effect of T. occidentalis seed extract and fractions on cardiac oxidative stress markers of rats with doxorubicininduced toxicity Treatment Dose mg/kg SOD (U/ml) CAT (U/g of protein) GPX (µg/ml) GSH (µg/ml) MDA (µMol/ml) Control 10 0.29± 0.01 1.86±0.02 0.056±0.003 2.57± 0.01 0.45± 0.01 Doxorubicin 1.66 0.18± 0.02a 1.42±0.08 0.050±0.005a 2.23± 0.01b 0.64± 0.02b Crude extract 138 0.20±0.03 2.32±0.38 0.050±0.003a 2.49± 0.14 0.47±0.01e 276 0.22±0.03 2.61±0.17 0.056±0.002d 2.50± 0.13 0.54±0.05 553 0.28±0.02d 3.42± 0.16a, f 0.056±0.002d 2.53± 0.12 0.58±0.02 Aqueous Fraction 276 0.28±0.03d 3.01±0.61e 0.049±0.005b 2.17± 0.01a 0.48± 0.04d DCM fraction 276 0.35±0.02f 2.36±0.16 0.067±0.008c, f 3.06± 0.04b, f 0.41± 0.05f Silymarin 100 0.28±0.02d 1.63±0.27 0.045±0.008c 2.38± 0.03a 0.47±0.01e Data are expressed as MEAN ± SEM, Significant at ap<0.05, bp<0.01, cp<0.001, when compared to control; Significant atdp<0.05, ep<0.01, fp<0.001 compared to organotoxic group. (n=5) Table 3 Effect of T. occidentalis seed extract and fractions on lipid profile parameters of rats with doxorubicin-induced toxicity Treatment Dose mg/kg Total cholesterol (MMOL/L) Triglyceride (MMOL/L) HDL-C (MMOL/L) LDL-C (MMOL/L) VLDL (MMOL/L) Control 10 3.33± 0.20 1.21±0.03 1.30±0.02 2.70± 0.22 0.56± 0.02 Doxorubicin 1.66 4.60± 0.15b 1.55±0.05c 1.60±0.06a 3.70± 0.09c 0.70± 0.02 Crude extract 138 3.80±0.11 1.31± 0.03e 1.44±0.01 2.95± 0.11e 0.60±0.01 276 3.33±0.23f 1.35±0.03d 1.45±0.04 2.49± 0.20f 0.61±0.01 553 2.63±0.17f 1.14±0.02f 1.23±0.04e 1.92± 0.13f 0.51±0.01e Aqueous Fraction 276 2.53±0.17f 1.08±0.07f 1.23±0.06e 1.78± 0.15a,f 0.49± 0.03e DCM fraction 276 2.40±0.17f 1.08±0.02f 1.19±0.07e 1.70± 0.14a,f 0.49± 0.04e Silymarin 100 3.00±0.28f 1.09±0.06f 1.20±0.07e 2.29± 0.24f 0.48± 0.04e Data are expressed as MEAN ± SEM, Significant at ap<0.05, bp<0.01, cp<0.001, when compared to control; Significant at dp<0.05, ep<0.01, fp<0.001 compared to organotoxic group. (n=5) GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 019-030 26 Figure 4 Photomicrographs of sections of hearts of rats treated with distilled water (CONT), doxorubicin only,1.66 mg/kg (T.CONT), Sylimarin,100 mg/kg and DOX(T+STD), T occidentalis, 138 mg/kg and DOX (T+LDE),T.occidentalis, 276 mg/kg and DOX (T+MDE), T.occidentalis, 553 mg/kg and DOX (T+HDE), Aqueous fraction,276 mg/kg and DOX (T+AQE) and DCM fraction, 276 mg/kg and DOX (T+DCME) showing well-presented cardiac myocytes (Cm), myocyte nuclei (Mn), fibrocyte nuclei (Fn) and endomysium (En) and blood vessels (Bv),inter-muscular vascular hemorrhage (red arrow) and fibrosis (black arrow) (H&E x 100) 4. Discussion Doxorubicin (DOX) is an anthracycline glycoside antibiotic with potent anticancer activity [27], whose clinical usefulness has been marred by irreversible and dose-dependent cardiomyopathy, nephrotoxicity and hepatotoxicity induced by the drug despite having a high therapeutic index [2]. DOX alters structural and functional processes due to its high affinity to phospholipids in the mitochondrial membrane in the cardiac cells [1] , thus resulting in nucleic acid damage, sarcomere disruption, and myofibril loss [28]. These undesirable effects have been traced to the activities of its metabolite, DOX-semiquinone, which reacts with O2, producing H2O2 and O2− (superoxide) [3], and inhibits the GSC Biological and Pharmaceutical Sciences, 2025, 33(01), 019-030 27 activities of endogenous enzymatic and nonenzymatic antioxidants thereby creating oxidative stress with damaging effect on the heart compared with other organs such as the kidney and liver [3,4]. This study was designed to assess the antitoxicant potentials of seed extract and fractions of Telfairia occidentalis against DOX-induced cardiotoxicity. The intraperitoneal administration of DOX showed cardiomyopathy manifested by raised levels of CK-MB, troponin I, and LDH and are consistent with earlier studies [29]. It has been observed that the mortality rate in animals treated with DOX was 40% compared with the normal control group before the end of experiment which may be due to accumulation of ascites resulting from abnormality in cardiac functioning [30]. Ascites is thought to developed due to extracellular volume expansion and fluid leakage towards interstitium due to tubular disorder and sodium retention as proposed in previous studies [31]. Co-administration of the seed extract of T. occidentalis in this study was observed to reduce the levels of troponin I, LDH and CK-MB, portraying a significant cardioprotective activity. This activity can be attributable to the free radicals scavenging activities of the phytochemical constituents of the seed extract as reported previously [8,9,13]. Reactive oxygen species generation, inflammatory processes and lipid peroxidation have been suggested to be responsible for doxorubicin-induced cardio and hepatotoxicity [32,33]. The findings of this study show that administration of doxorubicin (1.66 mg/kg, i.p) on alternate days for 14 days to rats caused significant decreases (p<0.05) in levels of enzymatic and non-enzymatic endogenous antioxidants (SOD, CAT, GPx and GSH) in the heart and elevated level of MDA when compared to control. Lipid peroxidation is a marker of oxidative stress and elevations in the amount of malondialdehyde (MDA), a lipid peroxidation product, have been reported following Dox treatment [34,35,36]. Similar trend was observed in this study. Coadministration of seed extract and fractions of T. occidentalis (138 - 553 mg/kg) with doxorubicin caused significant (p<0.05-0.001) non-dosedependent elevation in the levels of the antioxidant enzymes (SOD, CAT, GPx) when compared to control. Similarly, GSH level was significantly (p<0.001) elevated following treatment with the extract when compared to control. Similarly, there were significant (p<0.05-0.01) reductions in the level of MDA of the extract-treated rats. It has been documented that DOX inhibits the activities of endogenous enzymatic and nonenzymatic antioxidants as was the case in this study. So, an imbalance between ROS generation and neutralization leads to oxidative stress and injury to the heart [3,4,28]. The seed extract potentials to reduce the level of MDA shows a reduction in lipid peroxidation and generation of free radicals which might have been scavenged by the phytoconstituents present in this extract, hence the protective effect on the heart. Histological sections of rat hearts treated with doxorubicin alone showed section with degenerating cardiac muscle fibers which is a manifestation of the effect of doxorubicin toxicity due to the effect of free radicals generated by the drug. However, co-administration of T. occidentalis seed extract/fractions and doxorubicin reduced the effect of doxorubicin as was seen in mild effect to absent of pathological signs confirming the cardioprotective effect of Telfairia occidentalis seed. This effect can be attributed to the antioxidant activities of the phytochemical constituents of the seed extract such as the monoterpenes and polyunsaturated fatty acid (PUFA) previously reported in this seed extract which have been documented to exert antioxidant activities [8]. However, doxorubicin was found to raised significantly the levels of total cholesterol, triglyceride, HDL, LDL and VLDL. This result is consistent with that of Okokon et al. [37]. However,this portrays a serious risk to the heart and also indicates lipolysis promotion activity of the drug which leads to increase in the lipid profile parameters. Increases in lipid profile parameters have been linked to heart diseases [38]. The reduction of the raised levels of total cholesterol, triglycerides, VLDL, LDL and HDL in this study reveals a strong hypolipidemic activity of the seed extract and fractions perhaps due to inhibitory activity on lipolysis which is due to the activities of its phytoconstituents. This further confirms the cardioprotective potentials of the seed extract and fractions This effect can be attributed to the antioxidant activities of the phytochemical constituents of the seed extract previously reported in this seed extract which have been documented to exert antioxidant activities [8]. 5. Conclusion The findings of this study show that the seed extract and fractions of Telfairia occidentalis have the potentials to counteract the injurious effect of doxorubicin on the heart. This activity can be attributed to the antioxidant and antioxidative stress activities of its phytochemical constituents. Thus, the seed can be use to alleviate and/or prevent doxorubicin-induced cardiotoxicity.