Hepatoprotective effects of Ficus racemosa stem bark against carbon tetrachloride-induced hepatic damage in albino rats

In the present study, the hepatoprotective effects of petroleum ether (FRPE) and methanol (FRME) extract of Ficus racemosa Linn. (Moraceae) stem bark were studied using the model of hepatotoxicity induced by carbon tetrachloride (CCl₄) in rats. CCl₄ administration induced a significant decrease in serum total protein, albumin, urea and a significant increase (P?≤?0.01) in total bilirubin associated with a marked elevation in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) as compared to control rats. Further, CCl₄ intoxication caused significant increase in the TBARS and decrease in glutathione (GSH) levels in serum, liver and kidney. Pretreatment with FRPE and FRME restored total protein and albumin to near normal levels. Both the extracts resulted in significant decreases in the activities of AST, ALT and ALP, compared to CCl₄-treated rats. However, a greater degree of reduction was observed in FRME pretreated group (FRPE 43%, 38%, and 33%; FRME 55%, 73%, and 38%). Total bilirubin content decreased from 2.1?mg/dL in CCl₄-treated rats to 0.8 and 0.3?mg/dL in FRPE and FRME pretreated rats, respectively. The extracts improved the antioxidant status considerably as reflected by low TBARS and high GSH values. FRME exhibited higher hepatoprotective activity than a standard liver tonic (Liv52), while the protective effect of FRPE was similar to that of Liv52. The protective effect of F. racemosa was confirmed by histopathological profiles of the liver. The results indicate that F. racemosa possesses potent hepatoprotective effects against CCl₄-induced hepatic damage in rats.     

Telmisartan ameliorates carbon tetrachloride‐induced acute hepatotoxicity in rats

This study assessed the potential hepatoprotective effect of telmisartan (TLM), a selective angiotensin II type 1 (AT₁) receptor blocker, on carbon tetrachloride (CCl₄)‐induced acute hepatotoxity in rats. Intraperitoneal injection of male Wistar rats with CCl₄ 1 mL kg^?1, 1:1 mixture with corn oil for 3 days increased serum alanine transaminase, aspartate transaminase, and alkaline phosphatase activities as well as total bilirubin, triglycerides and total cholesterol levels. This is in addition to the disrupted histological architecture in the CCl₄ group. Rats receiving CCl₄ and co‐treated with TLM (3 and 10 mg kg^?1, orally) showed ameliorated serum biochemical and histological changes almost to the control level. Nevertheless, rats treated with TLM (1 mg kg^?1) didn't show any significant changes compared to CCl₄ intoxicated group. In addition, TLM rectified oxidative status disrupted by CCl₄ intoxication. Interestingly, TLM protected against CCl₄‐induced expressions of nuclear factor‐κB, inducible nitric oxide synthase and cyclooxygenase‐II, in a dose related manner. Moreover, TLM (3 and 10 mg kg^?1) significantly modified CCl₄‐induced elevation in tumor necrosis factor‐α and nitric oxide levels. Furthermore, TLM showed a marked decline in CD68+ cells stained areas and reduced activity of myeloperoxidase enzyme compared to CCl₄‐intoxicated group. In conclusion, both doses of TLM (3 and 10 mg kg^?1) showed significant hepato‐protective effects. However, TLM at a dose of 10 mg kg^?1 didn't show significant efficacy above 3 mg kg^?1 which is nearly equivalent to the human anti‐hypertensive dose of 40 mg. Thus, may be effective in guarding against several hepatic complications due to its antioxidant and anti‐inflammatory activities. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 359–370, 2017.     

Effect of Aerva lanata against hepatotoxicity of carbon tetrachloride in rats

The partially purified petroleum ether extractable fraction of the whole plant Aerva lanata (PF) was evaluated for the protective effect against liver damage induced by carbon tetra chloride (CCl₄) in Sprague Dawley rats. Rats were orally administered with PF (50 and 100 mg/kg body weight) for 14 days before CCl₄ challenge and 100 mg of PF alone for toxicity analysis without CCl₄ administration. The results showed that CCl₄ administration significantly damaged the liver as evident from histopathology and very high activity of serum and liver marker enzymes. It also reduced the antioxidant enzyme status of the animals. PF administration significantly reversed the histopathological changes and restored the elevated activities of liver marker enzymes and also enhanced the antioxidant enzyme activities. The extract also reduced hepatic lipid peroxidation and increased the serum total protein and albumin/globulin (A/G) ratio. Preliminary phytochemical analysis of PF showed the presence of alkaloids. These observations clearly indicate that PF contains antioxidant alkaloids capable of ameliorating the CCl₄-induced hepatic injury by virtue of its antioxidant activity.     

Hepatoprotective and antioxidant effects of baicalin against CCl4-induced hepatotoxicity

Scutellaria baicalensis is widely cultivated in eastern Asia, particularly in China. In the present study, we isolated baicalin from this plant and studied for its hepatoprotective activity against CCl₄-induced oxidative damage in rats. Our findings revealed that baicalin exhibited strong antioxidant activity in vitro. In established in vivo tests, baicalin showed effective protective effects by reducing the elevated levels of glutamate pyruvate transaminase(ALT), aspartate aminotransferase(AST), alkaline phosphatase (ALP), total bilirubin (TB) and malondialdehyde (MDA) against CCl₄-induced damage, and it restored the activities antioxidant defense substances, such as superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH), toward their normal levels. These data were supplemented with histopathological examination of rat liver sections. The results demonstrated that baicalin could be proposed to protect the liver against CCl₄-induced oxidative damage in rats, and the possible underlying mechanism of the activity could be due to its free radical-scavenging and antioxidant activity.     

Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats

Carbon tetrachloride (CCl4) is a model for studying free radical-induced liver injury and screening hepato-protective drugs. Numerous studies have reported the involvement of oxidative stress in CCl4-induced liver damage and the hepato-protective effects mediated by different antioxidants. The present study examined the effects of diphenyl diselenide, (PhSe)2, on hepatotoxicity induced by CCl4 in rats. To this end, male Wistar rats received (PhSe)2 by oral route at the dosage of 31.2 mg/kg for one or two days. After the second day of treatment, rats received CCl4 orally in a single dose. The liver and kidney were utilized for determination of histopathology, biochemical [aspartate (ALT) and alanine (AST) aminotransferases, alkaline phosphatase (ALP), total bilirrubin (TB) and gamaglutamyl transferase (GGT)] and toxicological parameters [thiobarbituric reactive species (TBARS) levels, catalase activity, ascorbic acid, nonprotein thiols (NPSH) and aminolevulinate dehydratase (-ALA-D) activity]. Repeated administration of (PhSe)2 caused a marked potentiation of hepatotoxicity induced by CCl4 exposure, as manifested by an increase in biochemical parameters (AST, ALT, ALP, GGT and BT) and severe alteration in histopathology. This study also demonstrated a potentiation of TBARS levels and a consequent depletion of important antioxidant defenses including catalase and ascorbic acid. Pre-treatment with a single dose of (PhSe)2 prevented the effect of strychnine, a substrate for CYPs, abolishing lethality in mice. This result indicates that (PhSe)2 prevented animal death, suggesting an activator action of (PhSe)2 in CYPs. This study clearly indicates that (PhSe)2 potentiated acute hepatic damage induced by CCl4.     

Hepatoprotective activity of Leptadenia reticulata stems against carbon tetrachloride-induced hepatotoxicity in rats

Objective:

To evaluate the hepatoprotective activity of ethanolic and aqueous extract of stems of Leptadenia reticulata (Retz.) Wight. and Arn. in carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats.

Materials and Methods:

The toxicant CCl₄ was used to induce hepatotoxicity at a dose of 1.25 ml/kg as 1 : 1 mixture with olive oil. Ethanolic and aqueous extracts of L. reticulata stems were administered in the doses of 250 and 500 mg/kg/day orally for 7 days. Silymarin (50 mg/kg) was used as standard drug. The hepatoprotective effect of these extracts was evaluated by the assessment of biochemical parameters such as serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, total bilirubin, serum protein, and histopathological studies of the liver.

Results:

Treatment of animals with ethanolic and aqueous extracts significantly reduced the liver damage and the symptoms of liver injury by restoration of architecture of liver as indicated by lower levels of serum bilirubin and protein as compared with the normal and silymarin-treated groups. Histology of the liver sections confirmed that the extracts prevented hepatic damage induced by CCl₄ showing the presence of normal hepatic cords, absence of necrosis, and fatty infiltration.

Conclusion:

The ethanolic and aqueous extracts of stems of L. reticulata showed significant hepatoprotective activity. The ethanolic extract is more potent in hepatoprotection in CCl₄-indiced liver injury model as compared with aqueous extract.     

玉郎伞皂苷对四氯化碳诱导大鼠肝纤维化的影响

目的研究玉郎伞皂苷(YLSS)对四氯化碳(carbontetrachloride,CCl4)所致大鼠肝纤维化的药理作用,并探讨其作用机制。方法将SD大鼠随机分成模型组及空白对照组(NC),模型组大鼠以50%CCl4食用油溶液为诱导剂灌胃造模,NC组灌胃给予食用油。将病理检查确认形成肝纤维化的SD大鼠,随机分成模型对照组(MC)和药物干预组。药物干预组分为4小组,分别灌胃给予YLSS(20、40和80mg.kg-1)及秋水仙碱片(0.20 mg.kg-1),模型组给予等剂量NS,连续给药4周。末次给药24 h后处死大鼠,采集血清及肝组织,检测大鼠血清中AST、ALT活性,测定肝组织中SOD、MDA、GSH和GSH-Px的含量,并观察肝组织病理学改变。结果各剂量YLSS和阳性药能降低大鼠血清中CCl4所致异常升高的AST、ALT水平(P<0.01),提高肝组织SOD、GSH含量(P<0.01),并降低异常升高的MDA含量(P<0.05或P<0.01);各剂量YLSS能升高大鼠肝组织GSH-Px(P<0.01);中、高剂量YLSS及阳性药能够减轻肝细胞损伤程度(P<0.01)。结论玉郎伞皂苷对CCl4诱导的大鼠肝纤维化具有一定的抑制作用,其机制可能与其清除自由基、抑制脂质过氧化有关。     

Hepatoprotective effects of diethylcarbamazine in acute liver damage induced by carbon tetrachloride in rats

This research was carried out to determine a potential role of leukotrienes in the acute hepatotoxicity induced by CC14 in rats. An inhibitor of leukotrienes biosynthesis, diethylcarbamazine (DEC, 25 and 50 mg ·kg-1 ip) exerted hepatoprotective effects, decreasing the activity of alanine aminotransfer-ase in serum and the concentration of liver triglycerides. DEC reduced histological damage of liver evidenced by electron microscopy. The hepatoprotective effects of DEC were dose-dependent. The results favor the role of leukotrienes in CC14 hepatotoxicity.     

地顶孢霉菌丝体对四氯化碳所致小鼠急性肝损伤的保护作用

目的 研究地顶孢霉菌丝体(AMM)对四氯化碳(CCl4)所致小鼠急性肝损伤的保护作用.方法 建立CCl4诱导的小鼠急性肝损伤模型;观察AMM对血清中ALT和AST活性的影响及AMM对肝组织SOD、MDA、GSH-PX表达水平和肝、脾、胸腺指数的影响;HE染色观察AMM对CCl4小鼠肝脏形态学影响.结果 AMM(1 00...     

Lipoic acid attenuates Aroclor 1260‐induced hepatotoxicity in adult rats

The present study was aimed to investigate the mechanistic aspect of Aroclor 1260‐induced hepatotoxicity and its protection by lipoic acid. The adult male Albino rats were divided into six groups. Group I served as control. Group II received lipoic acid (35 mg/kg/day). Aroclor 1260 was given to rats by oral gavage at doses 20, 40, or 60 mg/kg/day (Groups III, IV, and V, respectively). Group VI was pretreated with lipoic acid (35 mg/kg/day) 24 h before Aroclor 1260 (40 mg/kg/day). Treatment in all groups was continued for further 15 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities and total bilirubin, total cholesterol, and triglycerides were significantly increased while total protein, total albumin, and high‐density lipoprotein were significantly decreased. Hydrogen peroxide production and lipid peroxidation were significantly increased while superoxide dismutase and catalase activities and reduced glutathione (GSH) content was significantly decreased in liver. Caspase‐3 & ‐9 activities were significantly increased in liver. Lipoic acid pretreatment significantly reverted all these abnormalities toward their normal levels. In conclusion, Aroclor 1260 induced liver dysfunction, at least in part, by induction of oxidative stress. Apoptotic effect of hepatic cells is involved in Aroclor 1260‐induced liver injury. Lipoic acid could protect rats against Aroclor 1260‐induced hepatotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 913–922, 2016.     

Hepatoprotective effect of ginsenoside Rg1 from Panax ginseng on carbon tetrachloride‐induced acute liver injury by activating Nrf2 signaling pathway in mice

Oxidative stress and inflammatory response are well known to be involved in the pathogenesis of acute liver injury. This study was performed to examine the hepatoprotective effect of ginsenoside Rg1 (Rg1) against CCl₄‐induced acute liver injury, and further to elucidate the involvement of Nrf2 signaling pathway in vivo and in vitro. Mice were orally administered Rg1 (15, 30, and 60 mg/kg) or sulforaphane (SFN) once daily for 1 week prior to 750 μL/kg CCl₄ injection. The results showed that Rg1 markedly altered relative liver weights, promoted liver repair, increased the serum level of TP and decreased the serum levels of ALT, AST and ALP. Hepatic oxidative stress was inhibited by Rg1, as evidenced by the decrease in MDA, and increases in GSH, SOD, and CAT in the liver. Further research demonstrated that Rg1 suppressed liver inflammation response through repressing the expression levels of inflammation‐related genes including TNF‐α, IL‐1β, IL‐6, COX‐2, and iNOS. In addition, Rg1 enhanced antioxidative stress and liver detoxification abilities by up‐regulating Nrf2 and its target‐genes such as GCLC, GCLM, HO‐1, NQO1, Besp, Mrp2, Mrp3, Mrp4, and down‐regulating Cyp2e1. However, the changes in Nrf2 target‐genes, as well as ameliorative liver histology induced by Rg1 were abrogated by Nrf2 antagonist all‐transretinoic acid in vivo and Nrf2 siRNA in vitro. Overall, the findings indicated that Rg1 might be an effective approach for the prevention against acute liver injury by activating Nrf2 signaling pathway.     

"抗纤汤"治疗四氯化碳致肝纤维化大鼠模型的实验研究

目的观察"抗纤汤"对四氯化碳致肝损伤的肝纤维化大鼠模型的治疗效果.方法 60只大鼠被随机分为3组,每组20只,在治疗组用"抗纤汤"治疗3个月后分别比较正常对照组、模型组和治疗组大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、Ⅲ型前胶原(PCⅢ)、透明质酸(HA)的含量,并观察其组织学改变的差异.结果治疗组血清ALT、AST、PCⅢ、HA均显著低于模型组(P＜0.05).病理学提示,治疗组肝细胞损伤、肝脏脂肪变性与纤维组织形成较少.结论 "抗纤汤"在抗纤维化治疗中有确切疗效.     

GC‐MS‐based metabolomics reveals mechanism of action for hydrazine induced hepatotoxicity in rats

Gas chromatography–mass spectrometry (GC‐MS) has great advantages for analyzing organic/amino acids, which are often targets in efficacy and/or toxicity studies. Although GC‐MS has been used for the detection of many metabolic disorders, applications of GC‐MS‐based metabolomics in pharmacology/toxicology are relatively underdeveloped. We intended to investigate applicability of a GC‐MS‐based metabolomics approach for toxicological evaluation, and tried to elucidate the mechanism of hydrazine‐induced hepatotoxicity. Rats were administered hydrazine chloride orally (120 and 240 mg kg^?1), and urine, plasma and liver samples were collected at 24 or 48 h post‐dosing. Conventional clinical chemistry and liver histopathology were performed, urine and plasma were analyzed by GC‐MS, and metabolic profiles were assessed using chemometric techniques. Principal component analysis score plots showed clear separation of the groups, indicating dose‐dependent toxicity and recovery. The mechanism of toxicity was investigated based on semi‐quantification data of identified metabolites. Amino acid precursors of glutathione (cystein, glutamate and glycine) and a product of glutathione metabolism (5‐oxoproline) were elevated dose‐dependently, accompanied with elevation of ascorbate levels. In addition, intermediates of the TCA cycle were decreased, whereas participants of the urea cycle and other amino acids were increased. These alterations were associated with histopathological changes such as fatty degeneration and glycogen accumulation. Application of GC‐MS‐based metabolomics revealed that oxidative stress and GSH consumption play important roles in the etiology of hydrazine‐induced hepatotoxicity, demonstrating that this approach is a useful tool in pharmacology and toxicology for screening, elucidating mode of action and biomarker discovery. Copyright © 2010 John Wiley & Sons, Ltd.     

Hepatotoxicity and nephrotoxicity in rats induced by carbon tetrachloride and the protective effects of Teucrium polium and vitamin C

This work investigated the protective effects of Teucrium polium (T. polium) and vitamin C (Vit C) against carbon tetrachloride (CCl₄) induced hepatotoxicity and nephrotoxicity in rats. T. polium reduced the Fer reduced antioxidant power (FRAP) (IC₅₀?=?0.89?mg/ml) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) (IC₅₀?=?0.049 µg/ml) than Vit C, FRAP (IC₅₀?=?0.71?mg/ml) and DPPH (IC₅₀?=?0.029 µg/ml). Male albino Wistar rats were divided into six groups: Group I was used as controls, Group II received CCl₄ in olive oil (0.5?ml/kg) by gavage, Group III received CCl₄ in olive oil (0.5?ml/kg) by gavage after 3 d of receiving T. polium (5?g/l), orally, Group IV received T. polium (5?g/l) alone, by gavage, for 7 d, Group V received CCl₄ in olive oil (0.5?ml/kg) by gavage after 3 d of receiving Vit C (250?mg/kg) by gavage and Group VI received Vit C (250?mg/kg) alone by gavage. CCl₄ showed an increase of serum hepatic and renal markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine. Moreover, we noted an increase of lipid peroxidations and a decrease in antioxidants enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) of CCl₄ rats compared to controls. The pretreatment with (200?mg/kg) of T. polium and with Vit C (250?mg/kg) by gavage, for 7 d, displayed their ability to protect against oxidative damage and biochemical changes induced by CCl₄. Our results were in accordance with histopathological observations.     

Hepatoprotective effects of polymethoxyflavones against acute and chronic carbon tetrachloride intoxication

In the present study, we explore the protective effects of Citrus aurantium L. extract (CAE) against acute and chronic CCl₄-induced hepatotoxicity. The quantitative analysis of CAE was performed using HPLC-UV to determine the nobiletin content was approximately 27%. For the acute model, the male ICR mice were orally treated with water, silymarin (positive control, 200 mg/kg) and CAE (50 and 200 mg/kg) for 3 days prior to CCl₄ (1 mL/kg, 50% v/v in olive oil) IP injection. For the chronic model (n = 6/group), the mice were treated with each treatment for 28 consecutive days and CCl₄ (1 mL/kg, 20%) was injected twice a week. In both the acute and chronic models, the CCl₄ alone treated group showed histopathologic alterations with a significantly increase in serum hepatic enzyme levels together with a disrupted anti-oxidative status. In contrast, the CAE treatments restored pathologic alterations and recovered the oxidative status by enhancing antioxidant enzymes and reducing lipid peroxidation levels. Furthermore, CAE enhanced nuclear factor E2-related factor 2 (Nrf2) and its related cytoprotective signals, including NAD(P)H quinone oxidoreductase 1, UDP-glucuronosyltransferase, and γ-glutamylcysteine synthetase. Taken together, the present study demonstrates that CAE exerts a protective effect against CCl₄-induced hepatotoxicity with its anti-oxidant, anti-inflammatory, and anti-apoptotic activity.     

Hepatoprotective effects of Gentiana asclepiadea L. extracts against carbon tetrachloride induced liver injury in rats

This study is an attempt to evaluate the hepatoprotective activity of Gentiana asclepiadea L. against carbon tetrachloride-induced liver injury in rats. Methanol extracts of aerial parts (GAA) and roots (GAR) of G. asclepiadea at doses of 100, 200, and 400 mg/kg b.w. were orally administered to Wistar rats once daily for 7 days before they were treated with CCl₄. The hepatoprotective activity of the extracts in this study was compared with the reference drug silymarin. In CCl₄ treated animals, GAA and GAR significantly decreased levels of serum transaminases, alkaline phosphatase and total bilirubin, and increased the level of total protein. Treatment with the extracts resulted in a significant increase in the levels of catalase, superoxide dismutase and reduced glutathione, accompanied with a marked reduction in the levels of malondialdehyde, as compared to CCl₄ treated group. The histopathological studies confirmed protective effects of extracts against CCl₄-induced liver injuries. No genotoxicity was observed in liver cells after GAA treatment, while GAR showed only slight genotoxic effects by comet assay. Phytochemical analysis revealed the presence of sweroside, swertiamarin and gentiopicrin in high concentrations in both extracts. It could be concluded that the use of G. asclepiadea extracts in the treatment of chemical-induced hepatotoxicity.     

Protective effects of salecan against carbon tetrachloride-induced acute liver injury in mice

Carbon tetrachloride (CCl₄) is a well‐established model for screening hepato‐protective drugs. The aim of the present study was to evaluate the potential protective effects of a novel soluble β‐glucan salecan on acute liver injury induced by CCl₄ in mice and to further explore the underlying mechanisms. Mice were given salecan (40 mg kg^?1) or phosphate‐buffered saline for 3 days prior to treatment with a single intraperitoneal dose of CCl₄ (1 ml kg^?1 body weight). Animals were sacrificed at 0, 12, 24, 48, 72 and 96 h post‐injection of CCl₄. Serum liver enzyme levels, histology, lipid peroxidation, glutathione (GSH) content, expression of antioxidant enzymes and hepatocyte proliferation were subsequently evaluated. The serum levels of hepatic enzyme markers were markedly reduced in the salecan pretreatment group compared with the control group. Histopathological examination of the livers revealed that hepatocellular degeneration and necrosis were significantly attenuated at an early stage during CCl₄ intoxication and liver recovery was markedly accelerated at a later stage in salecan pre‐administered mice. Furthermore, salecan administration remarkably alleviated lipid peroxidation and restored GSH depletion. Meanwhile, the expression of antioxidant genes was significantly elevated in the salecan‐treated group. Interestingly, the administration of salecan remarkably enhanced hepatocyte proliferation in the recovery phase after CCl₄ injection. Taken together, these results demonstrated that salecan exhibits a protective action on acute hepatic injury induced by CCl₄ through attenuating oxidative stress and accelerating hepatocyte regeneration. Copyright © 2011 John Wiley & Sons, Ltd.     

水飞蓟宾-磷脂酰胆碱复合物与水飞蓟宾对四氯化碳所致小鼠急性肝损伤保护作用的对比

目的比较水飞蓟宾 磷脂酰胆碱复合物 (SPC)与水飞蓟宾对四氯化碳所致的小鼠肝损伤的保护作用。方法 5 0只小鼠随机分成 5组 ,通过对对照组、给药组小鼠血清中天冬氨酸氨基转移酶 (AST)、丙氨酸氨基转移酶(ALT)及肝组织学观察 ,比较SPC与水飞蓟宾对四氯化碳所致小鼠肝损伤之预防作用的效果。结果水飞蓟宾和SPC均能降低小鼠血清ALT、AST活性 ,能减轻肝脏病理学变化 ,但以SPC作用最为明显。结论SPC对四氯化碳造成的急性肝损伤有明显的保护作用 ,SPC的作用强于水飞蓟宾。     

Crucial role of cytochrome P450 in hepatotoxicity induced by 2,3‐dimethoxy‐1,4‐naphthoquinone in rats

Quinone toxicity is induced by two principal mechanisms: arylation/alkylation and a redox cycle. We have previously shown that increases in intracellular levels of superoxide anion and cell death induced by 2,3‐dimethoxy‐1,4‐naphthoquinone (DMNQ), a redox cycling quinone, are enhanced by pretreatment of rat primary hepatocytes with cytochrome P450 inhibitors. This indicates a novel interaction of quinones with cytochrome P450, and is thus worthy of further investigation using an in vivo model. The aim of this study was to examine the effects of cytochrome P450 inhibitors on DMNQ‐induced hepatotoxicity in rats. When DMNQ was administered intraperitoneally, the activities of serum alanine aminotransferase and aspartate aminotransferase were found to increase in a dose‐dependent manner, indicating that hepatotoxicity was induced by treatment with DMNQ. Pretreatment with the cytochrome P450 inhibitors SKF‐525A (SKF), cimetidine and ketoconazole potentiated the DMNQ‐induced hepatotoxicity. The blood concentration of DMNQ was not affected by administration of SKF. Pretreatment with the antioxidant α‐tocopherol almost completely attenuated the hepatotoxicity induced by DMNQ and by the combination of DMNQ with SKF. Levels of reduced glutathione in the liver were decreased and levels of oxidized glutathione were increased by treatment with DMNQ. These effects were potentiated by pretreatment with SKF. DMNQ‐induced lipid peroxidation in the liver was also enhanced by pretreatment with SKF. Taken together, these results indicate that DMNQ‐induced hepatotoxicity is augmented by inhibition of cytochrome P450 and that this augmentation is due to the enhancement of oxidative stress. Copyright © 2010 John Wiley & Sons, Ltd.