PROTECTIVE EFFECTS OF GRAPE SEED PROANTHOCYANIDINS AND SELECTED ANTIOXIDANTS AGAINST TPA-INDUCED HEPATIC AND BRAIN LIPID-PEROXIDATION AND DNA FRAGMENTATION, AND PERITONEAL MACROPHAGE ACTIVATION IN MICE

1. The comparative protective abilities of a grape seed proanthocyanid in extract (GSPE) (25-100 mg/kg), vitamin C (100 mg/kg), vitamin E suc cinate (VES) (100 mg/kg) and beta-carotene (50 mg/kg) on 12-O-tetradec anoylphorbol-13-acetate (TPA)-induced lipid peroxidation and DNA fragm entation in the hepatic and brain tissues, as well as production of re active oxygen species by peritoneal macrophages, were assessed. 2. Tre atment of mice with GSPE (100 mg/kg), vitamin C, VES and beta-carotene decreased TPA-induced production of reactive oxygen species, as evide nced by decreases in the chemiluminescence response in peritoneal macr ophages by approximately 70%, 18%, 47% and 16%, respectively, and cyto chrome c reduction by approximately 65%, 15%, 37% and 19%, respectivel y, compared with controls. 3. GSPE, vitamin C, VES and beta-carotene d ecreased TPA-induced DNA fragmentation by approximately 47%, 10%, 30% and 11%, respectively, in the hepatic tissues, and 50%, 14%, 31% and 1 1%, respectively, in the brain tissues, at the doses that were used. S imilar results were observed with respect to lipid peroxidation in hep atic mitochondria and microsomes and in brain homogenates. 4. GSPE exh ibited a dose-dependent inhibition of TPA-induced lipid peroxidation a nd DNA fragmentation in liver and brain, as well as a dose-dependent i nhibition of TPA-induced reactive oxygen species production in periton eal macrophages. 5. GSPE and other antioxidants provided significant p rotection against TPA-induced oxidative damage, with GSPE providing be tter protection than did other antioxidants at the doses that were emp loyed. (C) 1998 Elsevier Science Inc.