This study investigated the protective mechanism of aqueous leaves extract of Eucalyptus obliqua (EOAE) in CCl4-mediated liver damage in Wistar rats. The animals were orally pretreated with either the extract (200 and 500 mg/kg) or vitamin C (200 mg/kg) for 10 days prior to the intraperitoneal administration of 3 mL/kg CCl4 (30% in olive oil). Subsequently, hepatic function, antioxidant and histological analyses were evaluated. The results showed that the CCl4-induced increases in the activities of ALT, ALP, AST and the concentrations of bilirubin, oxidized glutathione and malondialdehyde were significantly and dose-dependently reduced in the extract-treated rats. The extract also significantly improved the attenuated activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase as well as total protein, albumin and glutathione concentrations in the hepatotoxic animals. These improvements could be attributed to the phytoconstituents revealed by the GCMS analysis of the extract. The observed activities compared with that of vitamin C and are suggestive of hepatoprotective and antioxidant properties of EOAE and were also supported by the histological results. Overall, these data indicate that EOAE has a significant protective effect against acute CCl4-induced hepatotoxicity in rats, which may be due to its capability to fortify the antioxidant defense systems
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