Additive effect of alpha-tocopherol and ascorbic acid in combating ethanol-induced hepatic fibrosis.

To investigate the efficacy of combined administration of alpha-tocopherol (AT) and ascorbic acid (AA) in reducing ethanol-induced hepatotoxicity. Rats were maintained for 90 days and grouped as follows: I-control rats, II-ethanol, III-alpha-tocopherol, IV-ethanol+alpha-tocopherol, V-AA, VI-ethanol+ascorbic acid, VII-alpha-tocopherol+ascorbic acid, VIII-ethanol+alpha-tocopherol+ascorbic acid. At the end of the experimental period, markers of hepatic function, oxidative stress, and the expression of markers of inflammation and fibrosis were assayed. The markers of hepatic function, lipid peroxidation products, protein carbonyls, and the expression of nuclear factor kappa B, tumor necrosis factor alpha, transforming growth factor beta 1, cytochrome P4502E1, and collagen Type I were elevated after ethanol administration. All these parameters were reduced in the ethanol group administered AT and AA in combination. The activities of antioxidant enzymes which were reduced by ethanol administration were enhanced on combined administration of AT and AA. The reduction in hepatic fibrosis was almost 20% more in AT and AA co-administered group compared with AT and AA alone treated groups. Combined administration of fat soluble AT and water soluble AA was beneficial against ethanol-induced hepatotoxicity. This may be due to their different subcellular localizations.