S-Adenosylmethionine prevents hepatic tocopherol depletion in carbon tetrachloride-injured rats

In various experimental models, S-adenosylmethionine (SAMe) has been shown to reduce liver injury by preventing depletion of glutathione, one of the antioxidant systems that plays a critical role in defence against oxidative stress. On the other hand, α-tocopherol may be decreased in liver diseases, and treatment with this vitamin reduces liver injury in CCl₄-treated rats. Since there is a close relationship among the different antioxidant systems (mainly glutathione, α-tocopherol and ascorbic acid), we have assessed whether, as well as restoring hepatic glutathione content, SAMe has any effect on liver α-tocopherol and ascorbic acid levels in CCl₄-injured rats. Four groups of seven male Wistar rats treated for 9 weeks were studied: rats induced to cirrhosis with CCl₄, rats induced to cirrhosis plus SAMe administration (10 mgċkg^-1ċday^-1) and their respective controls. Liver samples were obtained for measuring levels of glutathione, α-tocopherol, ascorbic acid and thiobarbituric acid-reactive substances (TBARS), and hydroxyproline concentration as an index of collagen content. The hydroxyproline content was higher in CCl₄-injured rats than in the control group (4.4±1.8 and 1.1±0.3 μmol/g respectively; P < 0.05). In CCl₄-injured rats, SAMe administration decreased collagen content (2.7±1.0 μmol/g; P < 0.05) and TBARS, and corrected glutathione depletion. α-Tocopherol was significantly lower in CCl₄-injured rats than in controls (17.3±4.9 and 23.0±4.0 μmol/g respectively; P < 0.05). By contrast, α-tocopherol levels were similar (23.8±5.1 μmol/g) in CCl₄-injured rats receiving SAMe and in controls. In CCl₄-injured rats, liver ascorbic acid was decreased in comparison with controls (4.9±1.8 and 8.2±1.0 μmol/g respectively; P < 0.05), levels which were not replenished by SAMe (4.6±0.4 μmol/g). In conclusion, SAMe not only decreases fibrosis and protects against hepatic glutathione depletion, but has a further antioxidant effect of preventing α-tocopherol depletion in CCl₄-injured rats.