Direct in vivo Evidence of Protective Effects of Grape Seed Procyanidin Fractions and Other Antioxidants against Ethanol-Induced Oxidative DNA Damage in Mouse Brain Cells

Abstract

Ethanol is a principle ingredient of alcoholic beverages with potential neurotoxicity and carcinogenicity, and the ethanol-associated oxidative DNA damage in the central nervous system is well documented. The present work studied the possible protective effects of grape seed oligomer and polymer procyanidin fractions against ethanol-induced toxicity and compared these with resveratrol and other well-known antioxidants (ascorbic acid and vitamin E). By using the single cell gel electrophoresis (comet assay), a simple and sensitive technique for genotoxicity studies, the potential genotoxicity of acute and chronic ethanol administration in the different brain regions was investigated. Acute ethanol administration, at the dose of 2.5 or 5.0 g kg(-1) i.p., could induce significant DNA damage in cerebellum and hippocampus. Chronic administration of ethanol at the dose of 2.5 or 5.0 g kg-1 p.o. for 30 days could induce significant DNA damage in cerebellum, hippocampus, hypothalamus, and cortex, which could be auto-repaired at least 3 days after ethanol withdrawal. Oral administration of grape seed oligomer and polymer procyanidins and resveratrol (25, 50, and 100 mg kg(-1)) for 3 days before acute ethanol (5.0 g kg(-1), i.p.) or repeated administration of these substances together with ethanol (5.0 g kg(-1), p.o.) for 30 consecutive days could significantly inhibit DNA damage in brain cells induced by ethanol. As compared, ascorbic acid (50, 100, and 200 mg kg(-1)) and vitamin E (100, 200, and 400 mg kg(-1)) could also present protective effects on ethanol-induced DNA damage. Furthermore, the concentrations of ethanol and acetaldehyde in brain regions of the mice were detected by gas chromatography after administration of ethanol plus antioxidants. All of the results indicated that ethanol could induce region-specific oxidative DNA damage in which the cerebellum and hippocampus were more vulnerable, but intake of grape seed procyanidins or other natural antioxidants could protect the brain against ethanol-induced genotoxicity.

Oligomer procyanidins (F2) isolated from grape seeds inhibits tumor angiogenesis and cell invasion by targeting HIF-1α in vitro

“…FPR1 is a membrane receptor overexpressed in U87 cells, regulates the cell growth, survival, migration and invasion (11,12). Moreover, an in vivo study showed that repeated administration of F2 to mice had no adverse effects (13). These data suggest that F2 may serve as a safe and efficient antitumor agent.…”

α-Tocopherol Protects Against Oxidative Stress in the Fragile X Knockout Mouse: an Experimental Therapeutic Approach for the Fmr1 Deficiency

“…There are previous works on daily systemic treatment with this antioxidant at a dose of 2350 mg/kg in monkeys to prevent toxicity. A recent publication demonstrated that a high dosage of tocopherol (100, 200, and 400 mg/kg) presented protective effects on ethanol-induced brain damage in mice (Guo et al, 2007).…”

Optimization of Extraction Process of Crude Protein from Grape Seeds by RSM

“…After processing, large amounts of grape seeds were produced as side product, so grape seeds were believed to be an alternative cheap source of proteins (Zhou et al, 2010). Grape seeds account for about 2-3% of the whole grape berry, and have received increasing attention for its significant health and other benefits (Del Bas et al, 2005;Al-Awwadi et al, 2005;Guo et al, 2007;Terra et al, 2007). Many studies mainly focus on the polyphenols of grape seeds (Nuno et al, 2004).…”