Attenuation of carbon tetrachloride-induced hepatic fibrosis by glycine, vitamin E and vitamin C -

Abstract

Objective: Mounting clinical and experimental evidence has demonstrated that even advanced fibrosis and cirrhosis are reversible. Thus, there is a considerable imperative to develop antifibrotic strategies that are applicable to liver fibrosis. In the present study, the attenuation of carbon tetrachloride (CCl 4 )-induced hepatic fibrosis in rats through the co-treatment with antioxidant vitamins C and E or glycine alone was investigated. Materials and Methods: Sixty male Sprague-Dawley were divided randomly into control, CCl 4 , vitamin E+C, and glycine groups. Except for the control group, all rats in the other groups received orally 2 ml/kg CCl 4 dissolved in olive oil (1:1, v/v) twice a week; antioxidant vitamins were supplemented orally (p.o.) at a dose of 200 IU/kg/day vitamin E and 50 mg/kg/day vitamin C. Glycine dose was 0.6 g/Kg/day (p.o.). After 9 weeks, all rats were sacrificed for biochemical and histopathological investigations. Results: Serum levels of hepatic transaminases, alkaline phosphatase, gamma glutamyl transferase, and β-glucuronidase strikingly increased in CCl 4 group. As a biomarker of fibrinogenesis, hyaluronic acid was significantly elevated. These were associated with drastic significant decline in serum albumin concentration level, blood glutathione (GSH) content, GSH peroxidase, catalase and superoxide dismutase enzymatic activities, as well as a striking significant increase in the concentration of serum malondialdehyde. A significant increase in the mean serum concentration levels of tumor necrosis factor-a and transforming growth factor-b1 has been observed in CCl 4 -treated rats. Histopathological examination highlighted and confirmed the biochemical results. Conclusion: The results of this study confirmed the ameliorative effects of vitamin E plus C combination and glycine supplements against liver fibrosis in rats induced by CCl 4 .