Free radicals and grape seed proanthocyanidin extract: importance in humanhealth and disease prevention

Free radicals have been implicated in over a hundred disease conditions in humans, including arthritis, hemorrhagic shock, atherosclerosis, advancing age, ischemia and reperfusion injury of many organs, Alzheimer and Parkinso n's disease, gastrointestinal dysfunctions, tumor promotion and carcinogene sis, and AIDS. Antioxidants are potent scavengers of free radicals and serv e as inhibitors of neoplastic processes. A large number of synthetic and na tural antioxidants have been demonstrated to induce beneficial effects on h uman health and disease prevention. However, the structure-activity relatio nship, bioavailability and therapeutic efficacy of the antioxidants differ extensively. Oligomeric proanthocyanidins. naturally occurring antioxidants widely available in fruits, vegetables: nuts, seeds, Bowers and bark, have been reported to possess a broad spectrum of biological, pharmacological a nd therapeutic activities against free radicals and oxidative stress. We ha ve assessed the concentration- or dose-dependent free radical scavenging ab ility of a novel IH636 grape seed proanthocyanidin extract (GSPE) both in v itro and in vivo models, and compared the free radical scavenging ability o f GSPE with vitamins C, E and beta-carotene. These experiments demonstrated that GSPE is highly bioavailable and provides significantly greater protec tion against free radicals and free radical-induced lipid peroxidation and DNA damage than vitamins C, E and beta-carotene. GSPE was also shown to dem onstrate cytotoxicity towards human breast, lung and gastric adenocarcinoma cells, while enhancing the growth and viability of normal human gastric mu cosal cells. The comparative protective effects of GSPE, vitamins C and E w ere examined on tobacco-induced oxidative stress and apoptotic cell death i n human oral keratinocytes. Oxidative tissue damage was determined by lipid peroxidation and DNA fragmentation, while apoptotic cell death was assesse d by flow cytometry. GSPE provided significantly better protection as compa red to vitamins C and E, singly and in combination. GSPE also demonstrated excellent protection against acetaminophen overdose-induced liver and kidne y damage by regulating bcl-X-L gene, DNA damage and presumably by reducing oxidative stress. GSPE demonstrated excellent protection against myocardial ischemia-reperfusion injury and myocardial infarction in rats. GSPE was al so shown to upregulate bcl(2) gene and downregulate the oncogene c-myc. Top ical application of GSPE enhances sun protection factor in human volunteers , as well as supplementation of GSPE ameliorates chronic pancreatitis in hu mans. These results demonstrate that GSPE provides excellent protection aga inst oxidative stress and free radical-mediated tissue injury. (C) 2000 Els evier Science Ireland Ltd. All rights reserved.