Antioxidant activity of the oyster mushroom, Pleurotus ostreatus, on CCl4-induced liver injury in rats

This study was undertaken to investigate the putative antioxidant activity of the oyster mushroom Pleurotus ostreatus on CCl₄-induced liver damage in male Wistar rats. Intraperitoneal administration of CCl₄ (2 ml/kg) to rats for 4 days resulted in significantly elevated (p < 0.05) serum levels of glutamic oxaloacetic transaminase (SGOT), glutamic pyruvate transaminase (SGPT) and alkaline phosphatase (SALP) compared to controls. In the liver, significantly elevated levels (p < 0.05) of malondialdehyde (MDA) and lowered levels (p < 0.05) of reduced glutathione (GSH) were observed following CCl₄ administration. Quantitative and qualitative analysis of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) revealed lower activities of these antioxidant enzymes in the liver of CCl₄-administered rats. An analysis of the isozyme pattern of these enzymes revealed variations in relative concentration presumably due to hepatotoxicity. When rats with CCl₄-induced hepatotoxicity were treated with the extract of P. ostreatus, the serum SGOT, SGPT and SALP levels reverted to near normal, while the hepatic concentration of GSH, CAT, SOD and Gpx were significantly increased (p < 0.05) and that of MDA significantly (p < 0.05) lowered, when compared to CCl₄-exposed untreated rats. Histopathological studies confirmed the hepatoprotective effect conferred by the extract of P. ostreatus. These results suggest that an extract of P. ostreatus is able to significantly alleviate the hepatotoxicity induced by CCl₄ in the rat.     

Protective effect of caffeic acid phenethyl ester against carbon tetrachloride-induced hepatotoxicity in mice

This study was designed to investigate the protective effects of the phenethyl ester of caffeic acid (CAPE) against carbon tetrachoride (CCl₄)-induced hepatotoxicities in mice. Pretreatment with CAPE prior to administration of CCl₄ significantly prevented the increases in serum alanine, aspartate aminotransferase and alkaline phosphatase activities, hepatic lipid peroxidation formation, and depletion of glutathione content. In addition, CAPE prevented CCl₄-induced apoptosis and necrosis, as indicated by liver histopathology and DNA laddering studies. To determine whether the Fas/Fas ligand (FasL) pathway is involved in CCl₄-induced acute liver injury, Fas and FasL proteins and caspase-3 and -8 activities were tested by western blotting and ELISA. CAPE markedly decreased CCl₄-induced Fas/FasL protein expression levels and, in turn, attenuated CCl₄-induced caspase-3 and -8 activities in mouse liver. Moreover, the effect of CAPE on CYP2E1, the major isozyme involved in CCl₄ bioactivation, was investigated. Treatment with CAPE significantly decreased the CYP2E1-dependent hydroxylation of aniline. In addition, CAPE attenuated the CCl₄-mediated depletion of antioxidant enzyme (catalase, superoxide dismutase and glutathione-S-transferase) activities. These findings suggest that the protective effects of CAPE against CCl₄-induced acute liver injury may involve its ability to block CYP2El-mediated CCl₄ bioactivation and to protect against Fas/FasL-mediated apoptosis.     

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.     

Central injection of astressin inhibits carbon tetrachloride-induced acute liver injury in rats

The effect of intracisternal astressin, a specific and potent corticotropin-releasing factor (CRF)₁ and CRF₂ receptor antagonist on carbon tetrachloride (CCl₄)-induced acute liver injury was investigated in rats. Intracisternal astressin inhibited the elevation of serum alanine aminotransferase level induced by CCl₄. Intracisternal astressin also reduced CCl₄-induced liver histological changes. The protective effect of central astressin on CCl₄-induced liver damage was abolished by sympathectomy but not by hepatic branch vagotomy. These findings demonstrate that astressin acts in the central nervous system to induce hepatic cytoprotection, possibly through the sympathetic pathways in rats. These results further establish a role of endogenous CRF in the brain in hepatic pathophysiological regulation.     

基于MAPK信号通路研究4-羟基苯并恶唑-2-酮抗肝纤维化的作用机制

目的： 探讨4-羟基苯并恶唑-2-酮（HBOA）对四氯化碳（CCl₄）诱导的大鼠肝纤维化的保护作用。方法： 采用CCl₄橄榄油溶液灌胃建立大鼠肝纤维化模型。第8周确定建模成功后,将雄性SD大鼠随机分成正常对照组,模型对照组,秋水仙碱阳性药组,HBOA高、中、低药物组。从第9周起,相应药物干预4周后,测定血清中总蛋白（TP）,白蛋白（Alb）的含量以及肝组织中羟脯氨酸（Hyp）的含量;免疫组织法检测肝组织中α-平滑肌肌动蛋白（α-SMA）蛋白含量的表达;Westerns blot法检测肝组织中MAPK,P-MAPK,P38的蛋白含量的表达。结果： 与模型组相比,HBOA可降低肝纤维化大鼠血清TP、Alb水平（P<0.01）以及肝组织中Hyp水平（P<0.01）,HBOA高中低剂量组显著降低大鼠肝组织中的α-SMA蛋白的表达（P<0.01）,并显著下调MAPK,P-MAPK,P38的蛋白表达水平（P<0.01）。结论： HBOA对CCl₄诱导的肝纤维化大鼠有一定的改善作用,通过抑制MAPK的信号通路,显著减轻了CCl₄诱导的纤维化。     

黄精通过氧化应激和线粒体凋亡途径保护CCl4诱导的大鼠急性肝损伤

研究黄精(Polygonatum sibiricum,PS)对CCl4诱导的大鼠肝损伤的保护作用及其抗氧化机制.采用一次性腹腔注射50％四氯化碳油溶液建立大鼠急性肝损伤模型,用黄精水提物(PSAE)灌胃治疗,水飞蓟素作为阳性对照药物,连续7天.PSAE显著降低了血清丙氨酸转氨酶、天冬氨酸转氨酶和碱性磷酸酶(AST、AL...     

Fucoidan partly prevents CCl4-induced liver fibrosis

Fucoidan, a sulfated polysaccharide extracted from brown algae, has a wide range of biological activities, including anti-inflammatory, anti-viral, and anti-tumor activities. In the present study, we investigated the effects of fucoidan on CCl₄-induced liver fibrosis. Administration of fucoidan reduced CCl₄-induced acute and chronic liver failure. Hepatic fibrosis induced by CCl₄ was also attenuated by injection of fucoidan. Damage to hepatocytes and activation of hepatic stellate cells are key events in liver fibrosis, and, interestingly, treatment of hepatocytes with fucoidan prevented CCl₄-induced cell death and inhibited the proliferation hepatic stellate cells. These results indicate that fucoidan might be a promising anti-fibrotic agent possessing dual functions, namely, protection of hepatocytes and inhibition of hepatic stellate cell proliferation.     

美洲大蠊提取物通过介导Nrf2/HO-1通路抑制氧化应激的抗肝纤维化作用

目的:探究美洲大蠊提取物(PA-B)对四氯化碳(CCl4)诱导的大鼠肝纤维化Nrf2/HO-1通路及氧化应激指标的影响.方法:采用腹腔注射40％ CCl4橄榄油溶液建立大鼠肝纤维化模型,48只大鼠随机分成正常对照组、肝纤维化模型组、秋水仙碱组、PA-B低剂量组、PA-B中剂量组、PA-B高剂量组,每组8只.治疗第4周末...     

Protein deficiency and muscle damage in carbon tetrachloride induced liver cirrhosis

Protein undernutrition, alterations of hormones such as IGF-1, testosterone and cortisol, and increased lipid peroxidation—which may be related with deranged metabolism of some elements such as iron (Fe), zinc (Zn), manganese (Mn), selenium (Se) or copper (Cu)—may contribute to muscle damage in non alcoholic cirrhosis. Here, we analyse the effect of protein deficiency on muscle Cu, Fe, Zn, Mn and Se in carbon-tetrachloride (CCl₄) induced liver cirrhosis. We also study the association between protein undernutrition and these trace elements with the activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and lipid peroxidation products, and how all these are related with muscle morphological changes in 40 male adult Sprague-Dawley rats. Liver cirrhosis was induced by intraperitoneal injection of CCl₄ to 10 rats fed a 2% protein diet, and to another 10 fed a 18% protein control diet. Two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. After sacrifice (6 weeks later), we found type IIa fibre atrophy in the cirrhotic animals, especially in the low-protein fed ones and this was due to protein deficiency. Muscle Fe increased in low protein fed cirrhotic rats. No relationship was found between muscle changes and any of the hormones, enzymes and trace elements analysed, or with liver fibrosis. These results suggest that muscle atrophy observed in CCl₄-induced cirrhosis is related with protein deficiency, but not with cirrhosis itself.     

异欧前胡素对四氯化碳致小鼠急性肝损伤的保护作用

目的：研究异欧前胡素对四氯化碳（CCl₄）诱导的小鼠急性肝损伤的保护作用。方法：60只昆明种小鼠随机分为正常对照（生理盐水）组、模型（生理盐水）组、水飞蓟宾（阳性对照,16 mg·kg^-1）组和异欧前胡素低、中、高剂量（8,16,32 mg·kg^-1）组,连续灌胃给药7 d,每天1次。末次给药1 h后,除正常对照组外其余各组小鼠腹腔注射0.1% CCl₄花生油溶液诱发小鼠急性肝损伤。16 h后摘眼球取血并处死小鼠,测定肝脏指数,检测血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）及肝组织中丙二醛（MDA）、超氧化物歧化酶（SOD）及谷胱甘肽（GSH）水平;检测肝脏线粒体中MDA水平、ATP酶活性及线粒体膜电位。结果：CCl₄诱导小鼠肝脏指数及血清ALT和AST水平显著升高,肝细胞肿胀、变性、坏死,出现明显炎性损伤;使肝组织及肝线粒体中MDA水平显著升高,SOD与GSH水平显著降低;同时导致肝线粒体中ATP酶活性显著降低,线粒体膜电位下降。而水飞蓟宾及异欧前胡素均可显著逆转CCl₄引发的这些效应。结论：异欧前胡素对CCl₄诱导的小鼠急性肝损伤具有保护作用,其机制可能与清除氧化应激产物MDA,增加细胞内抗氧化酶SOD与GSH活性及改善线粒体功能有关。     

Effects of the CCl 4 -cycloheximide interaction on protein synthesis and lipid metabolism in rat liver

A protective effect against triglyceride accumulation in liver was observed in CCl₄-poisoned rats pretreated with cycloheximide. This protection is not related to the action of cycloheximide on protein synthesis and secretion of triglyceride from liver into plasma in CCl₄-treated rats. The metabolism of CCl₄ is not affected by cycloheximide. Reduced levels of plasma free fatty acids in cycloheximide treated rats could explain the phenomenon, in spite of the behaviour of protein synthesis and triglyceride secretion.     

岩藻黄质调控TGF-β/Smad3信号通路减轻CCl4诱导的大鼠肝纤维化和氧化应激

目的： 探究岩藻黄质对肝纤维化模型大鼠氧化应激和纤维化的保护作用及可能机制。方法： 将雄性SD大鼠随机分为空白、模型、岩藻黄质和水飞蓟宾组。除空白组外,其余各组大鼠均皮下注射CCl₄溶液,2次/周,连续8周。造模同时,各组给予相应药物,空白和模型2组均给予等体积无菌水。8周后处死大鼠,检测血清谷草转氨酶（AST）、谷丙转氨酶（ALT）、总胆红素（T-BIL）、直接胆红素（D-BIL）、超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽-过氧化物酶（GSH-Px）、透明质酸（HA）、羟脯氨酸（HYP）、层粘连蛋白（LN）含量以及α-SMA、TGF-β/Smad3通路主要mRNA和蛋白表达;并检测肝组织病理变化和纤维化。结果： 与空白组比较,模型组大鼠血清AST、ALT、T-BIL、D-BIL、HA、HYP、LN、MDA,肝组织α-SMA mRNA和α-SMA、TGF-β、p-Smad3蛋白水平显著上调,而SOD和GSH-Px含量降低,肝脏可见细胞结构破坏,大量炎症细胞浸润,胶原沉积和纤维增生;与模型组相比,岩藻黄质和水飞蓟宾可显著逆转大鼠血清ALT、AST、T-BIL、D-BIL、HA、HYP、LN和MDA的升高及SOD和GSH-Px的降低,并缓解肝组织炎症和纤维化程度;此外,岩藻黄质可显著抑制肝组织α-SMA、TGF-β mRNA和α-SMA、TGF-β、p-Smad3蛋白表达水平。结论： 岩藻黄质通过抑制TGF-β/p-Smad3通路缓解大鼠肝纤维化水平,调节氧化应激状态。     

丹参多酚酸盐通过TGF-β1/Smad和PI3K/AKT/mTOR信号通路抑制大鼠肝纤维化的进展

目的：探索丹参多酚酸盐对四氯化碳诱导的大鼠肝纤维化的防治作用及其作用机制。方法：将雄性SD大鼠随机分为正常对照组（空白组）、CCl₄模型组（模型组）、丹参多酚酸盐低剂量组（低剂量组）和丹参多酚酸盐高剂量组（高剂量组）,每组12只。采用1 mL·kg^-1每周2次的剂量给予大鼠灌胃CCl₄-橄榄油（1：1）溶液诱导建立肝纤维化模型,治疗组大鼠在建模的同时分别每日1次腹腔注射丹参多酚酸盐15,30 mg·kg^-1。7周处死大鼠,观察大鼠肝脏大体形态;HE和Masson三色染色检测肝组织病理学变化;全自动生化分析仪检测大鼠肝功能指标,包括总胆红素（TBIL）、谷草转氨酶（AST）及谷丙转氨酶（ALT）;放射免疫法测定四项肝纤维化指标,包括透明质酸（HA）、层黏蛋白（LN）、Ⅲ型前胶原肽（PⅢP）和Ⅳ型胶原（CIV）;实时定量PCR法测定肝组织中α-SMA、MMP-1、TIMP-1、Collagen Ⅰ和Collagen Ⅲ基因表达的水平;Western blot检测肝脏组织中TGF-β1、Smad2/3、Smad7、p-PI3K、p-AKT、p-mTOR等蛋白的表达。结果：与模型组相比,丹参多酚酸盐能够显著降低大鼠肝功能和肝纤维化指标,并改善大鼠肝纤维化程度;与此同时,丹参多酚酸盐能够抑制肝组织中TGF-β1/Smad和PI3K/AKT/mTOR信号通路,且能够通过调节细胞外基质的合成和降解来抑制肝纤维化的进展。结论：丹参多酚酸盐可通过调节TGF-β1/Smad和PI3K/AKT/mTOR信号通路发挥抗肝纤维化的作用。     

Evaluation of sex difference in tissue repair following acute carbon tetrachloride toxicity in male and female Sprague–Dawley rats

Cellular regeneration and tissue repair greatly influence the outcome of acute carbon tetrachloride (CCl₄) hepatotoxicity. This study examined the temporal kinetics of cellular regeneration and tissue repair processes in male and female Sprague–Dawley (SD) rats following an acute CCl₄ exposure (0.8 ml/kg, i.p.). In female rats, hepatic damage peaked at 24 h following the treatment and was 2.5-fold (AST 2.7-fold, ALT 2.3 fold) greater than the damage observed in male rats. The hepatic damage in male rats appeared to peak by 3 h post-exposure and did not significantly change through the 36-h time-point. The activity of cytochrome P 4502E1 was 20% greater in male rats and did not correlate with the magnitude of hepatic damage. Morphometric analysis of cell cycle indices revealed that cellular regeneration was significantly greater in female rats as compared to male rats at 48 h and corresponded proportionally to the extent of liver damage. This study demonstrated that female SD rats respond more severely to acute CCl₄ hepatotoxicity than male SD rats and the extent of tissue repair and cellular regeneration was greater in female rats. Furthermore, our results suggest that tissue repair is unlikely to result in accounting for the different responses exhibited by male and female SD rats to CCl₄ hepatotoxicity.     

Protective effect of olive oil and colocynth oil against cadmium-induced oxidative stress in the liver of Wistar rats

Cadmium (Cd) is one of the most common heavy metal pollutants. It is accumulated particularly in liver and kidney. The present study examined the possible protective effect of olive oil and colocynth oil consumption against Cd-induced damage on plasma lipids and stress biochemical parameters of rats. Male albino Wistar rats were randomly divided into 6 groups of 5 animals each and treated orally with Cd (50 mg/l), olive oil and colocynth oil (4%) alone or in combination with cadmium for 8 weeks. It was shown that Cd exposure induced significant increases in the activities of serum alanine aminotransferase, aspartate aminotransferase, lipid peroxidation levels (MDA) and protein carbonyl contents in exposed groups of rats compared to control group while the antioxidant enzymes, reduced glutathione and vitamins (C, A and E) were significantly decreased. Co-treatment with olive oil or colocynth oil significantly improved the oxidative damage induced by Cd. The antioxidant potential in plasma and liver were markedly restored with a significant decline in MDA levels and activity of transaminases.In conclusion, these results suggest that olive oil or colocynth oil consumption could protect the rat liver against Cd-induced injury by increasing the activities of antioxidant enzymes and reducing oxidative stress.     

Hepatoprotective and antioxidant effects of Commiphora berryi (Arn) Engl bark extract against CCl(4)-induced oxidative damage in rats.

Oxidative damage is involved in the pathogenesis of various hepatic injuries. In the present study the capacity of Commiphora berryi (Arn) Engl bark as an antioxidant to protect against CCl(4)-induced oxidative stress and hepatotoxicity in Albino Wistar rats was investigated. Intraperitoneal injection of CCl(4), administered twice a week, produced a marked elevation in the serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin. Histopathological analysis of the liver of CCl(4)-induced rats revealed marked liver cell necrosis with inflammatory collections that were conformed to increase in the levels of SOD, GPx and CAT. Daily oral administration of methanolic extract of C. berryi (Arn) Engl bark at 100 and 200mg/kg doses for 15 days produced a dose-dependent reduction in the serum levels of liver enzymes. Treatment with C. berryi normalized various biochemical parameters of oxidative stress and was compared with standard Silymarin. Therefore, the results of this study show that C. berryi (Arn) Engl bark can be proposed to protect the liver against CCl(4)-induced oxidative damage in rats, and the hepatoprotective effect might be correlated with its antioxidant and free radical scavenger effects.     

Ketoprofen glucuronidation and bile excretion in carbon tetrachloride and alpha-naphthylisothiocyanate induced hepatic injury rats

A pharmacokinetic study was carried out in rats to investigate the effects of experimental hepatic injury on the liver glucuronidation and bile excretion of ketoprofen (KP) and its glucuronides (KPGs). In vivo, KP (20 mg/kg b.w.) was intravenously administered to carbon tetrachloride (CCl₄) or alpha-naphthylisothiocyanate (ANIT) induced hepatic injury male rats. Concentrations of KP and its glucuronides (S-KPG and R-KPG) in plasma and bile were determined by RP-HPLC. It was observed that there was significant difference in the accumulative bile excretion of KPGs between the CCl₄ intoxicated rats and the normal rats (54 ± 18.3% versus 90 ± 6.9%), while it was extremely inhibited in ANIT intoxicated rats (2.0 ± 3.1% versus 90 ± 6.9%). As the result of reduction of KPGs excreted in bile, the area under the curve (AUC_(0–∞)) of KP and KPGs were higher in blood in CCl₄ and ANIT hepatic injury rats than those of the normal rats. Specifically, ANIT caused approximately 10-fold elevation of AUC_(0–∞) of plasma S-KPG. In microsomal incubations experiment, the glucuronyltransferase activity was impaired in CCl₄ and ANIT intoxicated rats. It suggested that the glucuronyltransferase activity was impaired in CCl₄ and ANIT intoxicated rats, while the bile excretion function was suppressed extremely in ANIT intoxicated rats.     

吴茱萸碱复合纳米粒对急性肝损伤模型小鼠的保护作用

目的：探讨吴茱萸碱复合纳米粒（evodiamine complex loaded nanoparticles，ECNP）对四氯化碳（CCl₄）诱导的急性肝损伤模型小鼠的保护作用。方法：采用离子凝胶法制备ECNP，测定其粒径和电位。腹腔注射CCl₄复制小鼠急性肝损伤模型。评估ECNP和EVO干预对肝损伤小鼠血清指标AST、ALT、TNF-α、IL-1β和肝脏指数的影响；测定肝脏GSH、CAT、SOD水平和MDA含量。光镜下观察肝脏病理改变。结果：ECNP的粒径和电位分别为（435.30±24.70）nm和（43.43±0.50）mV。ECNP和EVO干预能降低小鼠肝脏指数，改善小鼠肝组织病理损伤，降低血清ALT、AST水平，减少炎症因子IL-1β、TNF-α的产生，增强肝组织抗氧化物SOD、GSH、CAT的能力；ECNP调节血清转氨酶、降低炎症因子、增加机体抗氧化能力的作用较等剂量的游离EVO更强。结论：ECNP对CCl₄致肝损伤有一定的保护作用，且比EVO效果更好。     

Metabolic Activation of PCBs to Carcinogens in Vivo - A Review

Our earlier studies have shown that extracts derived from potato peel (PPE) are rich in polyphenols and possess strong antioxidant activity both in vitro and in vivo. The objective of the present study was to investigate its potential to offer protection against acute liver injury in rats. Rats pretreated with PPE (oral, 100mg/kgb.w./day for 7 days) were administered a single oral dose carbon tetrachloride (CCl(4), 3ml/kg b.w., 1:1 in groundnut oil) and sacrificed 8h of post-treatment. Hepatic damage was assessed by employing biochemical parameters (transaminase enzyme levels in plasma and liver [AST-aspartate transaminase; ALT-alanine transaminase, LDH-lactate dehydrogenase]). Further, markers of hepatic oxidative damage were measured in terms of malondialdehyde (MDA), enzymic antioxidants (CAT, SOT, GST, GPX) and GSH (reduced glutathione) levels. In addition, the CCl(4)-induced pathological changes in liver were evaluated by histopathological studies. Our results demonstrated that pretreatment of rats with PPE significantly prevented the increased activities of AST and ALT in serum, prevented the elevation of hepatic MDA formation as well as protected the liver from GSH depletion. PPE pretreatment also restored CCl(4)-induced altered antioxidant enzyme activities to control levels. The protective effect of PPE was further evident through the decreased histological alterations in liver. Our findings provide evidences to demonstrate that PPE pretreatment significantly offsets CCl(4)-induced liver injury in rats, which may be attributable to its strong antioxidant propensity.     

Effects of salvianolic acid a on oxidative stress and liver injury induced by carbon tetrachloride in rats

In the present study, we investigated the hepatoprotective effects of salvianolic acid A, a novel antioxidant, against oxidative stress and acute liver injury induced by carbon tetrachloride (CCl(4)) in rats, and the mechanisms underlying its protective effects. Administration of CCl(4) to rats caused severe hepatic damage, as demonstrated by the significant increase in the levels of serum alanine aminotransferase, aspartate aminotransferase and classic histological changes including hepatocyte necrosis or apoptosis, haemorrhage, fatty degeneration, etc. Co-treatment with salvianolic acid A (20 mg/kg, intraperitoneally), a water-soluble extract from a Chinese traditional drug, Radix Salvia miltiorrhiza, significantly decreased CCl(4)-induced hepatotoxicity. Salvianolic acid A not only decreased serum alanine aminotransferase, aspartate aminotransferas levels and ameliorated histopathological manifestations in CCl(4)-treated rats, but also reduced oxidative stress, as evidenced by decreased reactive oxygen species production and malondialdehyde concentrations in the liver tissues, combined with elevated hepatic superoxide dismutase activity and gluthathione content. In addition, salvianolic acid A treatment remarkably reduced intrahepatic tumour necrosis factor-alpha concentrations and caspase-3 activities as compared with the CCl(4)-treated rats. The results suggested that treatment with salvianolic acid A provides a potent protective effect against acute hepatic damage caused by CCl(4) in rats, which may mainly be related to its antioxidative effect.