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The protective effects of the extract of Lycii fructus against hepatotoxicity of carbon tetrachloride (CCl4) were studied in rats. The rats were orally treated with CCl4 (50% in corn oil) at initial dose of 1 ml/kg followed by 0.5 ml/kg four times during 2-week period. The extract of L. fructus (50, 100 or 200 mg/kg) or its vehicle was administered everyday from 1 week before the start of CCl4 injection for five weeks. Exposure to CCl4 reduced red blood cells (RBC) and hemoglobin, whereas it markedly enhanced white blood cells (WBC). In addition, CCl4 induced hepatocelluar degeneration and necrosis, leading to a great increase in serum aspartate aminotransferase (AST), alanine aminotrasferase (ALT) and alkaline phosphatase (ALP) levels. In biochemical analyses, thiobarbituric acid-reactive substances (TBARS) and physphatidylcholine hydroperoxide (PCOOH) in hepatic tissues were remarkably increased by CCl4 treatment, resulting in the induction of antioxidant enzymes such as catalase and superoxide dismutase (SOD). Noteworthy, such changes in RBC, WBC and hemoglobin were recovered by treatment with the extract of L. fructrus to the control levels. In addition, not only increases in serum AST, ALT and ALP, but also induction of lipid peroxidation and antioxidant enzymes in hepatic tissues caused by CCl4 were significantly attenuated by the L. fructrus extract in a dose-dependent manner. Such hepato-protective effects of L. fructrus extract were confirmed by histopathological examinations, wherein only mild hepatocytic vacuolations were observed in the liver of rats treated with a high dose (200 mg/kg) of L. fructrus extract, in contrast to severe hepatocytic degenerations in rats administered with CCl4 alone. Taken together, it is suggested that the extract of Lycii fructus could be a promising candidate for the protection of liver injury, based on the preventive effects against morphological cellular injuries, lipid peroxidation and serum biochemical parameters.