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, alpha -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, alpha -tocopherol and ascorbic acid), we have assessed whether, as well as restoring hepatic glutathione content, SAMe has any effect on liver alpha -tocopherol and ascorbic acid levels in CCl4-injured rats. Four groups of seven male Wistar rats treated for 9 weeks were stud led : rats induced to cirrhosis with CCl4, rats induced to cirrhosis plus SAMe administration (10 mg.kg(-1).day(-1)) and their respective controls. Liver samples were obtained for measuring levels of glutathione, alpha -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 mu mol/g respectively; P < 0.05). In CCl4-injured rats, SAMe administration decreased collagen content (2.74 +/- 1.0 <mu>mol/g; P < 0.05) and TBARS, and corrected glutathione depletion. <alpha>-Tocopherol was significantly lower in CCl4-injured rats than in controls (17.3+/-4.9 and 23.0+/-4.0 mu mol/g respectively; P < 0.05). By contrast, <alpha>-tocopherol levels were similar (23.8+/-5.1 mu mol/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 mu mol/g respectively; P < 0.05), levels which were not replenished by SAMe (4.6+/-0.4 <mu>mol/g). In conclusion, SAMe not only decreases fibrosis and protects against hepatic glutathione depletion, but has a further antioxidant effect of preventing alpha -tocopherol depletion in CCl4-injured rats.