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 a ntioxidant systems that plays a critical role in defence against oxidative stress. On the other hand, alpha -tocopherol may be decreased in liver dise ases, and treatment with this vitamin reduces liver injury in CCl4-treated rats. Since there is a close relationship among the different antioxidant s ystems (mainly glutathione, alpha -tocopherol and ascorbic acid), we have a ssessed whether, as well as restoring hepatic glutathione content, SAMe has any effect on liver alpha -tocopherol and ascorbic acid levels in CCl4-inj ured rats. Four groups of seven male Wistar rats treated for 9 weeks were s tud led : rats induced to cirrhosis with CCl4, rats induced to cirrhosis pl us SAMe administration (10 mg.kg(-1).day(-1)) and their respective controls . Liver samples were obtained for measuring levels of glutathione, alpha -t ocopherol, ascorbic acid and thiobarbituric acid-reactive substances (TBARS ), and hydroxyproline concentration as an index of collagen content. The hy droxyproline content was higher in CCl4-injured rats than in the control gr oup (4.4+/-1.8 and 1.1+/-0.3 mu mol/g respectively; P < 0.05). In CCl4-inju red rats, SAMe administration decreased collagen content (2.74 +/- 1.0 <mu> mol/g; P < 0.05) and TBARS, and corrected glutathione depletion. <alpha>-To copherol 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, <alph a>-tocopherol levels were similar (23.8+/-5.1 mu mol/g) in CCl4-injured rat s 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 protec ts against hepatic glutathione depletion, but has a further antioxidant eff ect of preventing alpha -tocopherol depletion in CCl4-injured rats.