Ethanol inhibits δ-aminolevulinate dehydratase and glutathione peroxidase activities in mice liver: Protective effects of ebselen and N-acetylcysteine

Abstract

Changes in sulfhydryl status have been shown to be involved with the ethanol-induced hepatotoxicity. In addition, evidence shows the importance of replenishing thiols in patients with alcoholic liver disease. This study was undertaken to examine the possible beneficial effects of the individual and simultaneous treatments with two antioxidant drugs ( N-acetylcysteine and ebselen) against ethanol-induced changes in thiol status, as well as on the activities of δ-aminolevulinate dehydratase (δ-ALA-D) and glutathione peroxidase (GPx) in mice liver. Daily ethanol administrations (3 g ethanol/kg, by gavage) decreased liver nonprotein thiols (NPSH) concentration after 30 days of treatment and N-acetylcysteine (300 mg/kg once a day, i.p.) or ebselen (5 mg/kg once a day, subcutaneously) treatment restored this variable to control levels. However, additive beneficial effects concerning NPSH levels were not observed after the simultaneous administration with both drugs. While liver GPx and δ-ALA-D activities were inhibited by ethanol exposure and these inhibitions were significantly blunted by N-acetylcysteine or ebselen treatment, the simultaneous administration with both drugs did not show additive beneficial effects in relation to the enzymes’ activities. NPSH levels were positively correlated with GPx and δ-ALA-D activities. The results presented herein show that ebselen and N-acetylcysteine alone are able to restore ethanol-induced thiols as well as the inhibition of hepatic enzymes whose catalytic functions depend on their thiol (δ-ALA-D) and selenol (GPx) groups.