Hepatoprotective activities of picroliv, curcumin, and ellagic acid compared to silymarin on carbon-tetrachloride-induced liver toxicity in mice

Introduction:To evaluate the hepatoprotective activity of active phytochemicals, picroliv, curcumin, and ellagic acid in comparison to silymarin in the mice model of carbon tetrachloride (CCl4) induced liver toxicity. In addition, attempts were made to elucidate their possible mechanism(s) of action. Materials and Methods: Oxidative stress was induced in Swiss albino mice by a single injection (s.c.) of CCl4, 1 ml/kg body weight, diluted with arachis oil at a 1:1 ratio. The phytochemicals were administered once a day for 7 days (p.o.) as pretreatment at two dose levels (50 and 100 mg/kg/day). Results: CCl4-induced hepatotoxicity was manifested by an increase in the activities of liver enzymes (alanine transaminase, P<0.001, aspartate transaminase, P<0.001 and alkaline phosphatase, P<0.001), malondialdehyde (MDA, P<0.001)) levels and a decrease in activity of reduced glutathione (P<0.001) and catalase in liver tissues. The histopathological examination of liver sections revealed centrizonal necrosis, fatty changes, and inflammatory reactions. The pretreatment with picroliv, curcumin, and ellagic acid normalized serum aminotransferase activities (P<0.001), decreased levels of MDA (P<0.001), improved the antioxidant status, and normalized the hepatic histo-architecture. The restoration of phenobarbitone-induced sleeping time also suggested the normalization of liver cytochrome P450 enzymes. Conclusion: This study supports the use of these active phytochemicals against toxic liver injury, which may act by preventing lipid peroxidation, augmenting the antioxidant defense system or by regenerating the hepatocytes.