Protective effect of acteoside on carbon tetrachloride-induced hepatotoxicity

This study investigated the protective effects of acteoside, a phenylethanoid glycoside, on the carbon tetrachloride-induced hepatotoxicity as well as the possible mechanisms involved in this protection in mice. Pretreatment with acteoside prior to the administration of carbon tetrachloride significantly prevented the increased serum enzymatic activities of alanine and aspartate aminotransferase in a dose-dependent manner. In addition, pretreatment with acteoside significantly prevented the increase in hepatic malondialdehyde formation and the depletion of the reduced glutathione content in the liver of carbon tetrachloride-intoxicated mice. Carbon tetrachloride-induced hepatotoxicity was also essentially prevented, as indicated by a liver histopathologic study. The effects of acteoside on cytochrome P450 (P450) 2E1, the major isozyme involved in carbon tetrachloride bioactivation were also investigated. Treatment of the mice with acteoside resulted in a significant decrease in the P450 2E1-dependent pnitrophenol and aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the P450 2El protein levels were also lower. Acteoside exhibited anti-oxidant effects on FeCl2-ascorbate induced lipid peroxidation in a mouse liver homogenate, and on superoxide radical scavenging activity. These results suggest that the protective effects of acteoside against the carbon tetrachloride-induced hepatotoxicity possibly involve mechanisms related to its ability to block the P450-mediated carbon tetrachloride bioactivation and free radical scavenging effects.     

Protective effect of bixin on carbon tetrachloride-induced hepatotoxicity in rats

Background

The liver is an important organ for its ability to transform xenobiotics, making the liver tissue a prime target for toxic substances. The carotenoid bixin present in annatto is an antioxidant that can protect cells and tissues against the deleterious effects of free radicals. In this study, we evaluated the protective effect of bixin on liver damage induced by carbon tetrachloride (CCl₄) in rats.

Results

The animals were divided into four groups with six rats in each group. CCl₄ (0.125 mL kg^-1 body wt.) was injected intraperitoneally, and bixin (5.0 mg kg^-1 body wt.) was given by gavage 7 days before the CCl₄ injection. Bixin prevented the liver damage caused by CCl₄, as noted by the significant decrease in serum aminotransferases release. Bixin protected the liver against the oxidizing effects of CCl₄ by preventing a decrease in glutathione reductase activity and the levels of reduced glutathione and NADPH. The peroxidation of membrane lipids and histopathological damage of the liver was significantly prevented by bixin treatment.

Conclusion

Therefore, we can conclude that the protective effect of bixin against hepatotoxicity induced by CCl₄ is related to the antioxidant activity of the compound.     

Protective effect of C-phycocyanin against carbon tetrachloride-induced hepatocyte damage in vitro and in vivo

This study focused on the hepatoprotective activity of C-phycocyanin (C-PC) against carbon tetrachloride-induced hepatocyte damage in vitro and in vivo. In in vitro study, human hepatocyte cell line L02 was used. C-PC showed its capability to reverse CCl₄-induced L02 cells viability loss, alanine transaminase (ALT) leakage and morphological changes. C-PC also showed the following positive effects: prevent the CCl₄-induced overproduction of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA); prevent changes in superoxide dismutase (SOD) activity; and reduce glutathione (GSH) level. In vivo, C-PC showed its capability to decrease serum ALT and aspartate transaminase (AST) levels in CCl₄-induced liver damage in mice. The histological observations supported the results obtained from serum enzymes assays. C-PC also showed the following effects in mice liver: prevent the CCl₄-induced MDA formation and GSH depletion; prevent SOD and glutathione peroxidase (GSH-Px) activity; and prevent the elevation of transforming growth factor-beta1 (TGF-β1) and hepatocyte growth factor (HGF) mRNAs. Both the in vitro and in vivo results suggested that C-PC was useful in protecting against CCl₄-induced hepatocyte damage. One of the mechanisms is believed to be through C-PCs scavenging ability to protect the hepatocytes from free radicals damage induced by CCl₄. In addition, C-PC may be able to block inflammatory infiltration through its anti-inflammatory activities by inhibiting TGF-β1 and HGF expression.     

Hepatoprotective effect of Origanum vulgare in Wistar rats against carbon tetrachloride-induced hepatotoxicity

The effect of an aqueous extract of Origanum vulgare (OV) leaves extract on CCl₄-induced hepatotoxicity was investigated in normal and hepatotoxic rats. To evaluate the hepatoprotective activity of OV, rats were divided into six groups: control group, O. vulgare group, carbon tetrachloride (CCl₄; 2 ml/kg body weight) group, and three treatment groups that received CCl₄ and OV at doses of 50, 100, 150 mg/kg body weight orally for 15 days. Alanine amino transferase (ALT), alkaline phosphatase (ALP), and aspartate amino transferase (AST) in serum, lipid peroxide (LPO), GST, CAT, SOD, GPx, GR, and GSH in liver tissue were estimated to assess liver function. CCl₄ administration led to pathological and biochemical evidence of liver injury as compared to controls. OV administration led to significant protection against CCl₄-induced hepatotoxicity in dose-dependent manner, maximum activity was found in CCl₄?+?OV3 (150 mg/kg body weight) groups and changes in the hepatocytes were confirmed through histopathological analysis of liver tissues. It was also associated with significantly lower serum ALT, ALP, and AST levels, higher GST, CAT, SOD, GPx, GR, and GSH level in liver tissue. The level of LPO also decreases significantly after the administration of OV leaves extract. The biochemical observations were supplemented with histopathological examination of rat liver sections. Thus, the study suggests O. vulgare showed protective activity against CCl₄-induced hepatotoxicity in Wistar rats and might be beneficial for the liver toxicity.     

Protective effect of L-theanine on carbon tetrachloride-induced acute liver injury in mice

We studied effects of L-theanine, a unique amino acid in tea, on carbon tetrachloride (CCl(4))-induced liver injury in mice. The mice were pre-treated orally with L-theanine (50, 100 or 200 mg/kg) once daily for seven days before CCl(4) (10 ml/kg of 0.2% CCl(4) solution in olive oil) injection. L-theanine dose-dependently suppressed the increase of serum activity of ALT and AST and bilirubin level as well as liver histopathological changes induced by CCl(4) in mice. L-theanine significantly prevented CCl(4)-induced production of lipid peroxidation and decrease of hepatic GSH content and antioxidant enzymes activities. Our further studies demonstrated that L-theanine inhibited metabolic activation of CCl(4) through down-regulating cytochrome P450 2E1 (CYP2E1). As a consequence, L-theanine inhibited oxidative stress-mediated inflammatory response which included the increase of TNF-α and IL-1β in sera, and expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in livers. CCl(4)-induced activation of apoptotic related proteins including caspase-3 and PARP in mouse livers was also prevented by L-theanine treatment. In summary, L-theanine protects mice against CCl(4)-induced acute liver injury through inhibiting metabolic activation of CCl(4) and preventing CCl(4)-induced reduction of anti-oxidant capacity in mouse livers to relieve inflammatory response and hepatocyte apoptosis.     

Polyamines and thiols in the cytoprotective effect of L-cysteine and L-methionine on carbon tetrachloride-induced hepatotoxicity

Summary. The relationship between cellular glutathione (GSH), protein-SH levels, and lactate dehydrogenase (LDH), with respect to the effect of polyamines on the cytoprotective ability of L-cysteine and L-methionine, the most important components in the sulfur amino acid metabolic pathway, in carbon tetrachloride (CCl₄)-induced toxicity in isolated rat hepatocytes was studied. CCl₄ induced a LDH release and decreased cellular thiols and polyamines levels but treatment with L-cysteine and L-methionine reversed these decreases. Treating with methylglyoxal bis-(guanylhydrazone), MGBG, an irreversible inhibitor of S-adenosylmethionine decarboxylase, which is a key enzyme in spermidine and spermine biosynthesis, and therefore used to deplete cellular polyamines, prevented the protective effect of L-cysteine and L-methionine, but the addition of exogenous polyamines inhibited the influence of MGBG. These results suggest that the cytoprotective effect of L-cysteine and L-methionine in CCl₄-induced toxicity were via maintenance of cellular polyamines, GSH and protein-SH concentrations and prevention of LDH leakage. Received September 1, 1999, Accepted January 11, 2000     

Protective effect of cornuside against carbon tetrachloride-induced acute hepatic injury

This study elucidated the effects of cornuside on carbon tetrachloride (CCl?)-induced hepatotoxicity. Rats were treated intraperitoneally with 0.5 mL/kg of CCl?. Sixteen h after CCl? treatment, the levels of serum aminotransferases, tumor necrosis factor-α (TNF-α), and lipid peroxidation were significantly elevated, whereas the hepatic antioxidative enzyme activities were decreased. These changes were attenuated by cornuside. Histological studies also indicated that cornuside inhibited CCl?-induced liver damage. Furthermore, the contents of hepatic nitrite, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were elevated after CCl? treatment, while cytochrome P450 2E1 (CYP2E1) expression was suppressed. Cornuside treatment inhibited the formation of liver nitrite, and reduced the overexpression of iNOS and COX-2 proteins, but restored the liver CYP2E1 content as compared with the CCl?-treated rats. Our data indicate that cornuside protects the liver from CCl?-induced acute hepatotoxicity, perhaps due to its ability to restore the CYP2E1 function and suppress inflammatory responses, in combination with its capacity to reduce oxidative stress.     

Hepatoprotective effects of phosphatidylserine liposomes on carbon tetrachloride-induced hepatotoxicity in rats

It has been proposed carbon tetrachloride (CCl₄) intoxication due to the production of free radicals and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) overload results hepatotoxicity. Phosphatidylserine (PS) has shown antioxidant activity in numerous studies. Therefore, this study was aimed to investigate the effects of PS liposomes treatment against the CCl₄-induced hepatotoxicity in a rat model. Male Wistar rats were treated with PS (10 mg/kg, oral) or phosphatidylcholine liposomes (PC) (10 mg/kg, oral) for 3 days before CCl₄ (2 ml/kg; ip once on the third day) injection. The serum level of ALT, AST, and ALP were measured. Also, antioxidant assays were performed. Administration of PS with CCl₄ significantly inhibited alterations in the serum levels of AST, ALP (^**P < 0.01), and ALT (^***P < 0.001) compared with control group. Furthermore, measurement of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) levels indicated that PS significantly reduced reactive oxygen species. The results of the present study showed the hepatoprotective effects of PS against CCl₄-induced hepatotoxicity in rats.     

Protective effects of melatonin against carbon tetrachloride-induced hepatotoxicity in rats: a light microscopic and biochemical study

The aim of this study was to examine the protective effects of melatonin against CCl4-induced hepatotoxicity in the rat. Twenty-four male Wistar rats were divided into three groups. Group I was used as a control. Rats in group II were injected every other day with CCl4 for 1 month, whereas rats in group III were injected every other day with CCl4 and melatonin for 1 month. At the end of the experiment, all animals were killed by decapitation and blood samples were obtained. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and conjugated bilirubin levels were determined. For histopathological evaluation, livers of all rats were removed and processed for light microscopy. All serum biochemical parameters were significantly higher in animals treated with CCl4 than in the controls. When rats injected with CCl4 were treated with melatonin, significantly reduced elevations in serum biochemical parameters were found. In liver sections of the CCl4-injected group, necrosis, fibrosis, mononuclear cell infiltration, haemorrhage, fatty degeneration and formation of regenerative nodules were observed. Additionally, apoptotic figures, microvesicular steatosis and hydropic degeneration in hepatocytes were seen in this group. In contrast, the histopathological changes observed after administration of CCl4 were lost from rats treated with CCl4 and melatonin. Except for mild hydropic degeneration of the hepatocytes, a normal lobular appearance was seen in the livers of this group. The results of our study indicate that melatonin treatment prevents CCl4-induced liver damage in rats.     

Potentiation of carbon tetrachloride-induced hepatotoxicity and pneumotoxicity by pyridine

Induction of P450HE1 by pyridine was compared with that by ethanol, and the resulting potentiation of the pneumotoxicity and hepato-toxicity following carbon tetrachloride inhalation by pyridine was examined. Rats were treated with ethanol as either a 10% solution in the drinking water or as a daily bolus (3 ml/kg, ip) dose for 7 days or one bolus dose of pyridine (200 mg/kg, ip) and compared for P450IIE1 apoprotein content by immunoblot analysis. Ethanol in the drinking water and pyridine elevated both hepatic and pulmonary P450IIE1 apoprotein content, but bolus dose ethanol did not. The induction was greatest in the pyridine group. In the interaction study, rats were treated with pyridine (200 mg/kg, ip) and 12 hours later were exposed to CC1₄ (8000 ppm for 3 hours). Pulmonary injury and hepatic damage were assessed 24 hours later by bronchoalveolar lavage fluid (BALF) analysis [γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), and total protein] and serum sorbitol dehydrogenase (SDH) activity, respectively. Pyridine alone had no effect on BALF or SDH but enhanced GGT and LDH release into the BALF and SDH release into the serum when compared with CC1₄ exposure alone. Evaluation of the liver at the light microscopic level revealed characteristic CCl₄-induced centrilobular necrosis which was potentiated by pyridine. No changes were observed in the lung by light microscopic evaluation. Pyridine induced pulmonary and hepatic microsomal apoprotein levels of cytochrome P450IIE1 two- and 2- to sixfold, respectively. Exposure to CC1₄ decreased hepatic but not pulmonary P450IIE1 levels. Induction of cytochrome P450IIE1 by pyridine increases the bioactivation of CC1₄ in both the liver and lung, leading to enhanced toxicity.     

Protective effect of Phyllanthus fraternus against carbon tetrachloride-induced mitochondrial dysfunction.

The effect of carbon tetrachloride administration on liver mitochondrial function and the protective effect of an aqueous extract of Phyllanthus fraternus were studied in rats. The following changes were observed in mitochondria due to the administration of carbon tetrachloride. 1) A decrease in the rate of respiration, respiratory control ratio and P/O ratio using glutamate and malate or succinate as substrates. 2) A decrease in the activities of NADH dehydrogenase (35%), succinate dehydrogenase (76%) and cytochrome c oxidase (51%). The rate of electron transfer through site I, site II and site III was studied independently and found to be significantly decreased. 3) A decrease in the content of cytochrome aa3 (34%). 4) A significant decrease in the levels of phospholipids particularly cardiolipin and a significant increase in the lipid peroxide level was observed. The carbon tetrachloride induced toxicity may be partly due to the lipid peroxidation and partly due to the effect on protein synthesis. Administration of rats with an aqueous extract of P. fraternus prior to carbon tetrachloride administration showed significant protection on the carbon tetrachloride induced mitochondrial dysfunction on all the parameters studied.     

Effects of moderate copper deficiency on carbon tetrachloride-induced hepatotoxicity in rats.

Extreme copper deficiency has been shown to enhance CCl4-induced injury in rats. CCl4 hepatotoxicity was studied in rats with copper deficiency moderated by limiting deficiency periods to 5 or 6 weeks, using minimally adequate dietary zinc and including a marginal copper diet. Also, housing some rats in groups of six, rather than individually, was found to moderate the effects of low copper intake. Weanling male rats were fed copper at either 6, 2, or 0.2 mg/kg diet (adequate, marginal, deficient). Copper-zinc superoxide dismutase activity levels for singly and group-housed marginal rats were 80% and 93%, respectively, of adequate values. Values for deficient rats were 35% (singles) and 47% (group). In singly housed rats, a CCl4 dose of 400 microliters/kg intraperitoneally increased serum sorbitol dehydrogenase activities, indicators of cell membrane hepatotoxicity, in inverse proportion to dietary copper. A lower dose (100 microliters/kg) also produced smaller sorbitol dehydrogenase increases in adequate rats compared with deficients, but produced lowest increases in the marginals. The latter pattern also occurred in group-housed rats given the higher CCl4 dose, but the difference for adequate and marginal rats was not significant. The higher CCl4 dose, in singly housed rats, decreased liver glucose-6-phosphatase activities independently of copper intake. These activities are inversely proportional to microsomal lipid damage. In conclusion, moderate copper deficiency enhanced CCl4 hepatotoxicity, but the effect depended on injury criteria, CCl4 dose, and actual copper status as assessed by copper-zinc superoxide dismutase activities.     

Serum xanthine dehydrogenase of carbon tetrachloride-induced hepatotoxicity in alloxan-diabetic rats.

Xanthine dehydrogenase activity was determined in blood serum of rats in which diabetes had been induced by alloxan administration. The results show that there is no statistical significance in the difference found for normal and diabetic rats. Alloxan produced an inhibition in the enzyme activity in animals in which a carbon tetrachloride hepatotoxicity had been induced.     

Protective effect of the total flavonoids from <Emphasis Type="Italic">Apocynum venetum</Emphasis> L. on carbon tetrachloride-induced hepatotoxicity in vitro and in vivo

Apocynum venetum L., belonging to the family Apocynaceae, is a popular medicinal plant, which is commonly used in the treatment of hypertension, neurasthenia, and hepatitis in China. In the present study, the total flavonoids (TFs) were prepared from the leaves of A. venetum, and its protective effects on carbon tetrachloride (CCl₄)-induced hepatotoxicity in a cultured HepG2 cell line and in mice were investigated. Cell exposed to 0.4% CCl₄ (v/v) for 6 h led to a significant decrease in cell viability, increased LDH leakage, and intracellular reactive oxygen species (ROS). CCl₄ also induced cell marked apoptosis, which was accompanied by the loss of mitochondrial membrane potential (MMP). Pretreatment with TFs at concentrations of 25, 50, and 100 μg/mL effectively relieved CCl₄-induced cellular damage in a dose-dependent manner. In vivo, TFs (100, 200, and 400 mg/kg BW) were administered via gavage daily for 14 days before CCl₄ treatment. The high serum ALT and AST levels induced by CCl₄ were dose-dependently suppressed by pretreatment of TFs (200 and 400 mg/kg BW). Histological analysis also supported the results obtained from serum assays. Furthermore, TFs could prevent CCl₄-caused oxidative damage by decreasing the MDA formation and increasing antioxidant enzymes (CAT, SOD, GSH-Px) activities in liver tissues. In summary, both in vitro and in vivo data suggest that TFs, prepared from A. venetum, showed a remarkable hepatoprotective and antioxidant activity against CCl₄-induced liver damage.     

Protective effect of Aquilegia vulgaris (L.) on carbon tetrachloride-induced oxidative stress in rats

The ethyl ether extract of A. vulgaris inhibited in vitro microsomal lipid peroxidation (IC50 58.8 microg/ml) and showed moderate ability to scavenge superoxide radicals and to chelate iron ions. The extract (100 mg/kg body weight, po) decreased uninduced and enzymatic microsomal lipid peroxidation in the liver of male rats pretreated with CCl4 (1 ml/kg body weight) by 27 and 40%, respectively. Activity of antioxidant and related enzymes (catalase and glucose-6-phosphate dehydrogenase) inhibited by CCl4 was significantly restored after administration of the extract. The extract itself significantly enhanced superoxide dismutase activity. There was no effect of the extract on hepatic glutathione level and cytochrome P450 content, both were decreased by CCl4. Neither CCl4 nor the tested extract affected activities of NADPH-cytochrome P450 reductase and two monooxygenases, aniline hydroxylase and aminopyrine n-demethylase. It can be concluded that the protective effect of the A. vulgaris extract in CCl4-induced liver injury is mediated by inhibition of microsomal lipid peroxidation and restoring activity of some antioxidant and related enzymes.     

Protective effects of the apigenin-O/C-diglucoside saponarin from Gypsophila trichotoma on carbone tetrachloride-induced hepatotoxicity in vitro/in vivo in rats

This study investigated the hepatoprotective activity of saponarin, isolated from Gypsophila trichotoma Wend., using in vitro/in vivo hepatotoxicity model based on carbone tetrachloride (CCl₄)-induced liver damage in male Wistar rats. The effect of saponarin was compared with those of silymarin. In vitro experiments were carried out in primary isolated rat hepatocytes. Cell incubation with CCl₄ (86 μmol l⁻¹) led to a significant decrease in cell viability, increased LDH leakage, decreased levels of cellular GSH and elevation in MDA quantity. Cell pre-incubation with saponarin (60–0.006 μg/ml) significantly ameliorated CCl₄-induced hepatic damage in a concentration-dependent manner. These results were supported by the following in vivo study. Along with decreased MDA quantity and increased level of cell protector GSH, seven day pre-treatment of rats with saponarin (80 mg/kg bw; p.o.) also prevented CCl₄ (10%, p.o.)-caused oxidative damage by increasing antioxidant enzyme activities (CAT, SOD, GST, GPx, GR). Biotransformation phase I enzymes were also assessed. Administered alone, saponarin decreased EMND and AH activities but not at the same extent as CCl₄ did. However, pre-treatment with saponarin significantly increased enzyme activities in comparison to CCl₄ only group. The observed biochemical changes were consistent with histopathological observations where the hepatoprotective effect of saponarin was comparative to the effects of the known hepatoprotecor silymarin. Our results suggest that saponarin, isolated from Gypsophila trichotoma Wend., showed in vitro and in vivo hepatoprotective and antioxidant activity against CCl₄-induced liver damage.     

Mechanism of carbon tetrachloride-induced hepatotoxicity. Hepatocellular damage by reactive carbon tetrachloride metabolites

CCl4-induced liver damage was modeled in monolayer cultures of rat primary hepatocytes with a focus on involvement of covalent binding of CCl4 metabolites to cell components and/or peroxidative damage as the cause of injury. (1) Covalent binding of 14C-labeled metabolites was detected in hepatocytes immediately after exposure to CCl4. (2) Low oxygen partial pressure increased the reductive metabolism of CCl4 and thus covalent binding. (3) [14C]-CCl4 was bound to lipids and to proteins throughout subcellular fractions. Binding occurred preferentially to triacylglycerols and phospholipids, with phosphatidylcholine containing the highest amount of label. (4) The lipid peroxidation potency of CCl4 revealed subtle differences compared to other peroxidative substances, viz., ADP-Fe3+ and cumol hydroperoxide, respectively. (5) CCl4, but not the other peroxidative substances, decreased the rate of triacylglycerol secretion as very low density lipoproteins. (6) The anti-oxidant vitamin E (alpha-tocopherol) blocked lipid peroxidation, but not covalent binding, and secretion of lipoproteins remained inhibited. (7) The radical scavenger piperonyl butoxide prevented CCl4-induced lipid peroxidation as well as covalent binding of CCl4 metabolites to cell components, and also restored lipoprotein metabolism. The results confirm that covalent binding of the CCl3* radical to cell components initiates the inhibition of lipoprotein secretion and thus steatosis, whereas reaction with oxygen, to form CCl3-OO*, initiates lipid peroxidation. The two processes are independent of each other, and the extent to which either process occurs depends on partial oxygen pressure. The former process may result in adduct formation and, ultimately, cancer initiation, whereas the latter results in loss of calcium homeostasis and, ultimately, apoptosis and cell death.     

Protective effects of vitamin E on carbon tetrachloride-induced liver damage in rats

In this study we investigated whether the increase of hepatic vitamin E content by intraperitoneal administration, influences chronic liver damage induced by carbon tetrachloride (CCl(4)) in rats. Thirty adult male Wistar rats were divided into three groups. The first group was used as a control and the rats in the second group were administered CCl(4) in olive oil subcutaneously. Rats in the third group were administered intraperitoneally vitamin E (dl-alpha-tocopherol acetate, 100 mg kg(-1)). This administration was performed three times per week for five weeks. Liver samples were used for the determination of vitamin E levels, glutathione peroxidase (GSHPx) activities and histological examination. Serum levels of alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyltranspeptidase, total and conjugated bilirubin were significantly (p<0.05, p<0.01, p<0.001) higher in animals treated with CCl(4) than in the controls and had returned to normal values by the administration of vitamin E + CCl(4 ). Liver vitamin E levels were significantly (p<0.05) lower in the CCl(4) group than in the control group. However, the liver vitamin E content was significantly (p<0.01, p<0.001) increased in the vitamin E + CCl(4) injected group. On the other hand, liver GSHPx activity was not statistically different among the groups. On histological examination, vitamin E administered animals showed incomplete, but significant, prevention of liver necrosis and cirrhosis induced by CCl(4 ). these data indicate that intraperitoneally administered vitamin E has protective effects against CCl(4)-induced chronic liver damage and cirrhosis as evidenced by biochemical data and conventional histological examination.