CP-induced Rats Research Articles

Hepatoprotective effects of Alpinia officinarum rhizome extract on cisplatin-induced hepatotoxicity in rats: A biochemical, histopathological and immunohistochemical study

BackgroundAlpinia officinarum is a member of the ginger family (Zingiberaceae), which is widely cultivated in Asia and traditionally used for its anti-inflammatory, antimicrobial, and antihyperlipidemic qualities. This study aimed to evaluate the effect of Alpinia officinarum rhizome extract (AORE) on cisplatin (CP)-induced hepatotoxicity in rats. MethodsForty-four male rats were divided into six groups including the control group, AORE control group, CP control group, and three groups of CP (7 mg/kg dose, on the 10th day) with AORE (at concentrations of 100, 200 and 400 mg/kg, daily for 14 days). After 14 days, the rats' livers were removed and their liver function was assessed using biochemical marker enzymes including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) activities and albumin, total protein, and total bilirubin (T. bilirubin). Oxidative stress was assessed by evaluating malondialdehyde concentration and hepatic superoxide dismutase activity, histopathological and immunohistochemical tests were also conducted. ResultsResults demonstrated that treatment with AORE reduced the toxicity in levels of the hepatic biomarkers in cp-induced groups. AORE treatment decreased oxidative stress and improved histopathological indexes. Furthermore, immunohistochemical (IHC) investigation showed the B-cell lymphoma 2 (Bcl-2) upsurging and p53 downregulating expression exhibiting the recovery following AORE administration. ConclusionThe founding suggested that AORE administration has positive biochemical, histopathological, and immunohistochemical impacts on the ameliorating of hepatotoxicity in CP-induced rats.

Ginger's Antiapoptotic and Antioxidant Effects on Ovaries of Cyclophosphamide-therapied Rats.

In the recent decade, there has been increasing interest in preventing ovarian toxicity after chemotherapy exposure. It has been documented that ginger (Zingiber officinale) might normalize the hormonal balance and control the menstrual cycle.. This study has analyzed whether ginger extract protects against cyclophosphamide (CP)-induced ovarian failure in rats. Rats were distributed into four groups consisting of vehicle, CP, ginger, and CP + ginger. At the end of the treatment, all rats were killed under anesthesia to obtain ovarian tissues and blood samples for histological, molecular, and biochemical experiments. Our results indicated that ginger improves CP-caused histological changes in ovarian tissues and significantly restores serum hormonal abnormalities. Ginger also showed unique antioxidant, anti-inflammatory, and antiapoptotic properties in the ovarian tissues of CP-induced rats. Further, our findings indicated that ginger might activate the Nrf2 and SIRT and inhibit the PI3K/AKT pathway in the ovaries of CP-treated rats. In conclusion, ginger was found to protect against CP-caused ovarian toxicity in rats. The protective impacts of ginger may mediate, at least partly, by alleviating the oxidant state, inhibiting pro-inflammatory conditions, and exhibiting antiapoptotic activities.

Qiangjing tablets repair of blood-testis barrier dysfunction in rats via regulating oxidative stress and p38 MAPK pathway

BackgroundThe blood-testis barrier (BTB) is a physical barrier of the testis to prevent various exogenous substrates from entering apical compartments and provides immune privilege for spermatogenesis, which is essential for normal spermatogenic function of testis. It has been shown that oxidative stress can damage BTB by activating the p38 MAPK pathway. In Traditional Chinese Medicine, Qiangjing tablets (QJT) improve spermatogenesis and increase pregnancy rates. Previous studies have confirmed that QJT can improve sperm quality and have obvious antioxidant effects. In this study, we explore whether QJT contributes to recovery from BTB dysfunction in rats.MethodsBTB dysfunction was induced in rats by 1% Cyclophosphamide (CP). The CP-induced rats in the treatment group were given a dose of QJT (0.45 g/kg·d) by gavage. Testis tissues were collected for histopathological and biochemical analysis, and the testis weight was estimated. Levels of BTB-related proteins and antioxidant enzyme were analyzed in the testis tissues.ResultsQJT resolved the pathological injury of rats testis induced by CP. Furthermore, MDA levels were significantly reduced, and the levels of SOD markedly increased in the testicular tissue after QJT treatment. In addition, QJT down-regulated the expression of p38 protein in rat testis and up-regulated the expressions of key proteins ZO-1, occludin and F-actin in BTB.ConclusionThese results demonstrate that QJT exerts protective effects on CP-induced rats with BTB dysfunction, likely by regulating the oxidative stress-mediated p38 MAPK pathway.

Effect of cashew (Anacardium occidentale L.) nut-supplemented diet on steroidogenic enzymes, hormonal and oxidative imbalances, and sperm parameters in cisplatin-induced reproductive toxicity in male rats.

Cisplatin (CP) is a chemotherapeutic/anticancer drug culpable in sperm and testicular damage, but the use of dietary patterns has been reported to averse this effect. To date, no report on the use of roasted cashew nut-supplemented diets (RCNSD) against chemotherapy-induced testicular damage has been presented. In this study, the effect of 10% and 20% RCNSD on reproductive hormones, sperm parameters, testicular and epididymal antioxidant status, and steroidogenic enzymes activities in CP-induced rats were determined. Interestingly, these parameters were boosted, but with a decrement in radical species level in the testes/epididymis of CP-induced rats fed with RCNSD as against the untreated CP-induced rats. The modulatory effect of RCNSD on the tested reproductive parameters in studied tissues could be among the mechanism of action, by which RCNSD mitigates andrological toxicity. Hence, RCNSD could be harnessed as a functional food/nutraceutical agent for alleviating the andrological toxicity of CP-induced male reproduction. PRACTICAL APPLICATIONS: Consumption of cashew nuts has been a great benefit to human health, as a result of its richness in nutritional constituents including biologically active amino acids, tocopherols, fatty acids, polyphenols, and selenium, among others. Cashew nuts are mostly consumed fried/roasted, with yoghurt, as a paste, or used as an ingredient in confectionery products. The folkloric use of cashew nuts in the management of cardiovascular diseases, male reproductive disorders, and diabetes has been reported. In this study, the ability of roasted cashew nut-supplemented diets to modulate reproductive hormones, sperm parameters, testicular and epididymal antioxidant status, and steroidogenic enzymes activities in CP-induced reproductive toxicity in male rats was revealed, thus, indicating its possible use, clinically, in the management of reproductive toxicity induced by cancer drugs.

Edaravone mitigates hemorrhagic cystitis by modulating Nrf2, TLR-4/NF-κB, and JAK1/STAT3 signaling in cyclophosphamide-intoxicated rats.

Hemorrhagic cystitis is a potentially deadly complication associated with radiation therapy and chemotherapy. This study explored the protective effect of edaravone (ED) on cyclophosphamide (CP)-induced hemorrhagic cystitis, oxidative stress, and inflammation in rats. The animals received 20 mg/kg ED for 10 days and a single injection of 200 mg/kg CP on day 7. CP induced tissue injury manifested by the diffuse necrotic changes, disorganization of lining mucosa, focal hemorrhagic patches, mucosal/submucosal inflammatory cells infiltrates, and edema. CP increased malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha, and interleukin 6 (IL-6), decreased IL-10, and upregulated toll-like receptor 4 (TLR-4), nuclear factor-kappa B (NF-κB) p65, Janus kinase 1 (JAK1), and signal transducer and activator of transcription 3 (STAT3) in the urinary bladder of rats. ED effectively prevented the histopathological alterations, decreased MDA, NO, and inflammatory mediators, and downregulated TLR-4, NF-κB, JAK1, and STAT3 in CP-induced rats. Treatment with ED upregulated ikβ kinase β, IL-10, nuclear factor-erythroid 2 related factor 2 (Nrf2), and cytoglobin,and boosted glutathione, superoxide dismutase, and glutathione S-transferase. Molecular docking simulations revealed the ability of ED to bind TLR-4, NF-κB, JAK1, and STAT3. In vitro, ED increased the cytotoxic activity of CP against HeLa, Caco-2, and K562 cell lines. In conclusion, ED prevented CP-induced hemorrhagic cystitis in rats by attenuating oxidative stress, suppressing TLR-4/NF-κB, and JAK1/STAT3 signaling and boosted Nrf2, cytoglobin, and antioxidants.

The protective effect of Rubus fruticosus L. on blood composition in cyclophosphamide treated male rats

BackgroundSome chemotherapy drugs such cyclophosphamide (CP) has destructive effects on hematopoietic cells in the bone marrow tissue. Due to antioxidant and anti-inflammatory features, medicinal herbs have protective effects on the bone marrow tissue. The aim of this experimental study is to examine the protective effects of Rubus fruticosus L. extract (RF) on blood parameters in male rats treated with CP.MethodsIn this experimental study, 35 male Wistar rats (220–250 g) were randomly divided into 5 groups (n = 7): Control (0.5 mL normal saline), CP (15 mg/kg), positive control (RF per se 200 mg/kg), treatment 1 (CP 15 mg/kg + RF 100 mg/kg), and treatment 2 (CP 15 mg/kg + RF 200 mg/kg). All drugs and extracts were given intraperitoneally for 15 consecutive days. At the end of the intervention, all animals were euthanized and their blood samples were collected by cardiac puncture in anti-coagulant tubes for blood parameters evaluation.ResultsThe data analysis showed that CP has decreased significantly in RBC, WBC, Platelets number, hemoglobin and hematocrit in rats (p < 0.05). RF could protect hematopoiesis in CP-induced rats (p < 0.05).ConclusionThe use of RF can protect the blood hematopoietic tissue in bone marrow and prevent CP toxic effects.

&lt;p&gt;Edaravone and Acetovanillone Upregulate Nrf2 and PI3K/Akt/mTOR Signaling and Prevent Cyclophosphamide Cardiotoxicity in Rats&lt;/p&gt;

IntroductionCyclophosphamide (CP) causes redox imbalance and its use is associated with marked cardiotoxicity that limits its clinical applications. The present study investigated the protective effects of acetovanillone (AV) and edaravone (ED) against CP-induced oxidative stress and cardiac damage, emphasizing the role of PI3K/Akt/mTOR and Nrf2 signaling.Materials and MethodsRats received either AV (100 mg/kg) or ED (20 mg/kg) orally for 10 days and CP (200 mg/kg) on day 7. At day 11, the rats were sacrificed, and samples were collected for analysis.ResultsAV and ED ameliorated serum troponin I, CK-MB, LDH, AST and ALP, and prevented cardiac histological alterations in CP-intoxicated rats. Both treatments decreased cardiac lipid peroxidation and enhanced GSH, SOD and cytoglobin in CP-induced rats. AV and ED downregulated Keap1, whereas increased the expression of PI3K, Akt, mTOR and Nrf2 in the heart of rats received CP. Additionally, the binding modes of AV and ED to Keap1 were pinpointed in silico using molecular docking simulations.ConclusionAV and ED prevent CP cardiotoxicity by attenuating oxidative stress and tissue injury, and modulating cytoglobin, and PI3K/Akt/mTOR and Keap1/Nrf2 signaling. Therefore, AV and ED may represent promising agents that can prevent cardiac injury in patients receiving CP.

Human umbilical cord-derived mesenchymal stem cells and human cord blood mononuclear cells protect against cisplatin-induced acute kidney injury in rat models.

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are a promising tool to attenuate cisplatin (CP)-induced acute kidney injury (AKI). However, whether the transplantation of human cord blood mononuclear cells (hCBMNCs) exhibits similar protective effects and their potential underlying mechanisms of action remain unclear. The present study aimed to determine the protective effects of hUCMSCs and hCBMNCs transplantation therapies on an established CP-induced rat model and explore their underlying mechanisms of action. A total of 24 Sprague-Dawley rats, selected based on body weight, were randomly assigned into 4 groups: i) normal control; ii) model (CP); iii) hCBMNCs (CP + hCBMNCs); and iv) hUCMSCs (CP + hUCMSCs). hUCMSCs (2.0x106 cells) and hCBMNCs (2.0x106 cells) were injected into the femoral vein of rats 24 h after CP (8 mg/kg) treatment. To determine the effects of hCBMNCs and hUCMSCs on CP-induced rats, renal function assessment and histological evaluations were performed. Expression levels of high mobility group box 1 (HMGB1) and the ratio of Bax/Bcl2 in renal tissues were detected to elucidate their underlying molecular mechanisms of action. The results demonstrated that transplantation of hUCMSCs and hCBMNCs significantly improved renal function in CP-induced AKI rats, as evidenced by the enhancement of renal morphology; decreased concentrations of blood urea nitrogen and serum creatinine; and a lower percentage of apoptotic renal tubular cells. The expression of HMGB1 and the ratio of Bax/Bcl-2 were significantly reduced in the hUCMSCs and hCBMNCs groups compared with CP group. In conclusion, the present study indicated that hCBMNCs exert similar protective effects to hUCMSCs on CP-induced AKI. hUCMSCs and hCBMNCs protect against CP-induced AKI by suppressing HMGB1 expression and preventing cell apoptosis.

Galangin Activates Nrf2 Signaling and Attenuates Oxidative Damage, Inflammation, and Apoptosis in a Rat Model of Cyclophosphamide-Induced Hepatotoxicity.

Cyclophosphamide (CP) is a widely used chemotherapeutic agent; however, its clinical application is limited because of its multi-organ toxicity. Galangin (Gal) is a bioactive flavonoid with promising biological activities. This study investigated the hepatoprotective effect of Gal in CP-induced rats. Rats received Gal (15, 30 and 60 mg/kg/day) for 15 days followed by a single dose of CP at day 16. Cyclophosphamide triggered liver injury characterized by elevated serum transaminases, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and histopathological manifestations. Increased hepatic reactive oxygen species, malondialdehyde, nitric oxide, and oxidative DNA damage along with declined glutathione and antioxidant enzymes were demonstrated in CP-administered rats. CP provoked hepatic nuclear factor-kappaB (NF-κB) phosphorylation and increased mRNA abundance of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) both expression and serum levels. Gal prevented CP-induced liver injury, boosted antioxidants and suppressed oxidative stress, DNA damage, NF-κB phosphorylation and pro-inflammatory mediators. Gal diminished Bax and caspase-3, and increased B-cell lymphoma-2 (Bcl-2) in liver of CP-administered rats. In addition, Gal increased peroxisome proliferator-activated receptor gamma (PPARγ) expression and activated hepatic nuclear factor erythroid 2-related factor 2 (Nrf2) signaling showed by the increase in Nrf2, NAD(P)H: quinone acceptor oxidoreductase-1 (NQO-1) and heme oxygenase 1 (HO-1) in CP-administered rats. These findings suggest that Gal prevents CP hepatotoxicity through activation of Nrf2/HO-1 signaling and attenuation of oxidative damage, inflammation and cell death. Therefore, Gal might represent a promising adjuvant therapy to prevent hepatotoxicity in patients on CP treatment.

Hypolipidemic Effects of Pea Protein Hydrolysates on Lipid Profile and Uric Acid in Cisplatin-Induced Nephropathy Rats

The usage of Cisplatin (CP) can cause side effects such as toxicity and impaired kidneyfunction. Poor kidney function causes dyslipidemia and hyperuricemia. Researchers in Canadastate that pea protein hydrolysates can improve kidney function. The aim was to examine thehypolipidemic effect of 8 types of pea protein hydrolysate on lipid profiles and uric acid in CPinduced rats in purpose to find protein sources origin of Indonesia for kidney therapy. This is atrue experimental study using fifty female Wistar rats divided into 10 treatment groups.Weadministered 8 types of pea protein hydrolysate for 30 days. On day 7 all rats (except negativecontrol) were induced CP intraperitoneally. Study parameters was evaluated on days 12 and30. In general, all treatments showed good hypolipidemic effects, and differed significantly fromCP group (p &lt;0.01). The group that showed lowest total cholesterol, LDL and triglycerideresults is yellow pea protein hydrolysate Neutrase; HDL: green peas protein hydrolysatebromelain, uric acid: protein hydrolysate of pea protein isolate bromelain. As conclusion,protein hydrolysates of pea has good hypolipidemic effects on Lipid profile and Uric Acid inCP-induced nephropathy Rats.&#x0D; Keywords: protein hydrolysates, green peas, neutrase, bromelain, lipid profiles

Olea europaea leaf extract up-regulates Nrf2/ARE/HO-1 signaling and attenuates cyclophosphamide-induced oxidative stress, inflammation and apoptosis in rat kidney

Olive leaf extract (OLE) has potential health benefits and protects against cytotoxicity in different organs. However, nothing has yet been reported on its potential to prevent cyclophosphamide (CP)-induced nephrotoxicity. This study investigated the possible protective effect of OLE on CP-induced kidney injury in rats, focusing on oxidative stress, inflammation, apoptosis and Nrf2/ARE/HO-1 signaling. Rats received 100 or 200 mg/kg body weight OLE for 15 days and a single injection of 150 mg/kg CP at day 16. CP induced kidney injury evidenced by the significantly increased serum creatinine and urea, and histopathological alterations, including glomerular atrophy, interstitial hemorrhage, dilated urinary space and necrosis. CP-induced rats exhibited increased kidney lipid peroxidation, protein carbonyl, nitric oxide (NO) and pro-inflammatory cytokines, and up-regulated NF-κB, Bax, cytochrome c and caspase-3. OLE ameliorated kidney function markers and prevented CP-induced tissue damage. In addition, OLE significantly prevented oxidative stress, inflammation and apoptosis by enhancing the antioxidant defenses and Bcl-2 expression, and suppressing the pro-inflammatory and pro-apoptotic markers NF-κB, Bax, cytochrome c and caspase-3. OLE up-regulated Nrf2, HO-1 and NQO-1 expression in the kidney of CP-induced rats. In conclusion, OLE has a substantial protective role against CP-induced nephrotoxicity in rats by up-regulating the Nrf2/ARE/HO-1 signaling, enhancing the antioxidant activity and attenuating inflammation and apoptosis.

Role of pea protein hydrolysates as antinephrotoxicity

Introduction: Renal damage can be caused by various causes. One of them is drugs that are toxic to the renal, such as cisplatin (CP). In an attempt to find a remedy for antinephrotoxicity, several hydrolyzed proteins were investigated. This study was conducted to find out the effects of 8 peas protein hydrolysates (PPH) hydrolyzed using simple procedure to renal organ indexes (OIs) and histopathological features of CP-induced nephrotoxicity Wistar rats. Materials and Methods: Protein hydrolysates of yellow peas, gude beans, green peas, and pea protein isolate (PPI) which hydrolyzed using neutrase or bromelain were administered to 50 female Wistar rats. The treatments were given for 30 days, and on day 7, all groups of rats, except negative control group, were injected CP intraperitoneal. Renal OIs were measured and kidneys were histopathological analyzed, which the results were converted to scoring system. Data were analyzed using ANOVA, LSD, Kruskal–Wallis, and Mann–Whitney test. Results: Data of renal OIs were homogenous and normally distributed but were not significantly different between groups (P > 0.05).The nephrotoxicity of CP were not changing the renal OI but worsen the histopathological features of renal tubules in CP-induced rats (P < 0.01). All protein hydrolysate treatment groups showed less histopathological score than CP group. Green PPH hydrolyzed by bromelain-treatment group showed the lowest scores. Conclusion: All PPH hydrolized with neutrase or bromelain improve the CP-induced nephrotoxicity rats. Green PPH with bromelain hydrolyzed had a promising potency as antinephrotoxicity.

Characterization of Rubia cordifolia L. root extract and its evaluation of cardioprotective effect in Wistar rat model.

OBJECTIVES:Rubia cordifolia L. (RC) is a well-known and highly valuable medicinal plant in the Ayurvedic system. The present study involves evaluating antioxidant and cardioprotective property of RC root extract.MATERIALS AND METHODS:The characterization of RC root extract was carried out using standard phytochemical and biochemical analysis. The functional groups were analyzed by Fourier transform infrared (FTIR) spectroscopy and phytotherapeutic compounds were identified using high-resolution mass spectrometry (HR-MS). Cardioprotective activity of RC root extract was investigated against cyclophosphamide (CP; 100 mg/kg, i.p)-induced cardiotoxicity in male albino Wistar rats. RC (100, 200, and 400 mg/kg, p.o) or silymarin (100 mg/kg, p.o) was administered immediately after CP on the 1st day and the next consecutive 10 days. Biochemical and histopathological analysis was performed to observe the cardioprotective effects of RC root extract.RESULTS:Phytochemical analysis revealed the presence of secondary metabolites that include alkaloids, flavonoids, saponins, and anthraquinones in RC root extract. FTIR analysis revealed the presence of several functional groups. Based on HR-MS analysis, eight major phytotherapeutic compounds were identified in methanol root extract of RC. Biochemical analysis in CP-induced rat model administered with RC extract revealed significantly enhanced levels of antioxidant markers such as superoxide dismutase, catalase, and glutathione S-transferase. Histopathological study showed that the rat model treated with the root extract had reduced the cardiac injury.CONCLUSION:Our results have shown that the RC extract contains various antioxidant compounds with cardioprotective effect. Treatment with RC root extract could significantly protect CP-induced rats from cardiac tissue injury by restoring the antioxidant markers.

Possible involvement of Nrf2 and PPARγ up-regulation in the protective effect of umbelliferone against cyclophosphamide-induced hepatotoxicity.

Umbelliferone (UMB) is a coumarin derivative with promising hepatoprotective effects. In this study, we examined the possible protective effects of UMB against cyclophosphamide (CP)-induced hepatotoxicity, addressing the question of the possible role of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator activated receptor gamma (PPARγ). Wistar rats were orally administered UMB at doses 50 and 100mg/kg two weeks prior to CP injection. Five days after CP administration, the rats were sacrificed and samples were collected for analyses. CP induced a significant increase in circulating liver marker enzymes and pro-inflammatory cytokines. Hepatic lipid peroxidation and nitric oxide levels, and nuclear factor-kappaB (NF-κB) and inducible nitric oxide synthase (iNOS) expression were significantly increased following CP administration. UMB supplementation attenuated CP-induced inflammation and oxidative stress as assessed by restoration of the activity and expression of the antioxidant defenses, and suppression of pro-inflammatory cytokines. Histological examination also showed that UMB could significantly reduce CP-induced alterations. CP-induced rats showed significant down-regulation of Nrf2, HO-1 and PPARγ, an effect that was markedly reversed by UMB. In conclusion, the hepatoprotective effects of UMB appear to depend on co-activation of PPARγ and Nrf2, and subsequent suppression of oxidative stress and inflammation.

Gamma-Glutamylcysteine Ethyl Ester Protects against Cyclophosphamide-Induced Liver Injury and Hematologic Alterations via Upregulation of PPARγ and Attenuation of Oxidative Stress, Inflammation, and Apoptosis.

Gamma-glutamylcysteine ethyl ester (GCEE) is a precursor of glutathione (GSH) with promising hepatoprotective effects. This investigation aimed to evaluate the hepatoprotective effects of GCEE against cyclophosphamide- (CP-) induced toxicity, pointing to the possible role of peroxisome proliferator activated receptor gamma (PPARγ). Wistar rats were given GCEE two weeks prior to CP. Five days after CP administration, animals were sacrificed and samples were collected. Pretreatment with GCEE significantly alleviated CP-induced liver injury by reducing serum aminotransferases, increasing albumin, and preventing histopathological and hematological alterations. GCEE suppressed lipid peroxidation and nitric oxide production and restored GSH and enzymatic antioxidants in the liver, which were associated with downregulation of COX-2, iNOS, and NF-κB. In addition, CP administration significantly increased serum proinflammatory cytokines and the expression of liver caspase-3 and BAX, an effect that was reversed by GCEE. CP-induced rats showed significant downregulation of PPARγ which was markedly upregulated by GCEE treatment. These data demonstrated that pretreatment with GCEE protected against CP-induced hepatotoxicity, possibly by activating PPARγ, preventing GSH depletion, and attenuating oxidative stress, inflammation, and apoptosis. Our findings point to the role of PPARγ and suggest that GCEE might be a promising agent for the prevention of CP-induced liver injury.

Mitigation of oxidative stress in cyclophosphamide-challenged hepatic tissue by DL-α-lipoic acid

The present study investigated the protective effect of DL-alpha-lipoic acid on the tissue peroxidative damage and abnormal antioxidant levels in cyclophosphamide (CP) induced hepatotoxicity. Male Wistar rats of 140 +/- 20 g were categorized into four groups. Two groups were administered CP (15 mg/kg body weight once a week for 10 weeks by oral gavage) to induce hepatotoxicity; one of these groups received lipoic acid treatment (35 mg/kg body weight intraperitoneally once a week for 10 weeks; 24 h prior to the CP administration). A vehicle (saline) treated control group and a lipoic acid drug control group were also included. The extent of liver damage in CP-induced rats was evident from the increased activities of serum aminotransferases, alkaline phosphatase and lactate dehydrogenase; whereas lipoic acid pretreatment prevented the rise in these marker enzymes. We evaluated the changes in activities/levels of tissue enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase and glucose-6-phosphate dehydrogenase) and non-enzymic (reduced glutathione, ascorbate and a-tocopherol) antioxidants along with malondialdehyde levels in the experimental groups. In CP-administered rats the antioxidant enzymes showed significantly depressed activities (p < 0.001, p < 0.01) and the antioxidant molecules also showed depleted levels (p < 0.001, p < 0.01), in comparison with the control group. However the extent of lipid peroxidation and the abnormal antioxidant status were normalized in lipoic acid pretreated rats. The present work highlights the efficacy of lipoic acid as a cytoprotectant in CP-induced hepatic oxidative injury.