Resveratrol and trimethylated resveratrol protect from acute liver damage induced by CCl4 in the rat

The importance of hydroxyl groups in the antioxidant and hepatoprotective properties of resveratrol was investigated. To achieve this, resveratrol or its trimethylated analog were administered (10 mg kg(-1), p.o.)to male Wistar rats and liver damage was induced by acute administration of CCl4 (4 g kg(-1), p.o.); appropriate controls were performed. The animals were killed 24 h after CCl4 intoxication. The amount of reduced glutathione (GSH) in the liver was not modified by any treatment; interestingly, the GSH/GSSG (oxidized glutathione) ratio decreased in the groups receiving CCl4 and resveratrol associated with an increase in GSSG. In blood GSH and the GSH/GSSG ratio were decreased by CCl4; both effects were completely prevented by any of the compounds tested. Lipid peroxidation and the activity of gamma-glutamyl transpeptidase were increased significantly after CCl4. Resveratrol partially prevented these increases and surprisingly, trimethylated resveratrol completely prevented the increase of these markers. Both compounds partially but significantly prevented the increase in the activity of alanine aminotransferase; this result agrees with observations in the histological analysis. Both tested compounds administered alone produced no effect. The results of the present study suggest that OH groups are important for the antioxidant and hepatoprotective properties of the molecule of resveratrol; nevertheless, these effects can be improved by replacing hydrogen by a methyl in these groups. The differences in the antioxidant and hepatoprotective effects of these compounds could be due to the possibility that the trimethylated resveratrol acts like a prodrug, prolonging, probably, the half-life of the original compound. Copyright (c) 2007 John Wiley & Sons, Ltd.