Protective effect of vitamin e against ethanol-induced hyperhomocysteinemia, DNA damage, and atrophy in the developing male rat brain

Abstract

Background: Chronic alcoholism leads to elevated plasma and brain homocysteine (Hcy) levels, as demonstrated by clinical investigations and animal experiments. It has been posited that elevated levels of Hcy mediate DNA damage, brain atrophy, and excitotoxicity. The current study sought to elucidate the effect of vitamin E on ethanol-induced hyperhomocysteinemia, DNA damage, and atrophy in the developing hippocampus and cerebellum of rats. Methods: Pregnant Wistar rats received ethanol with or without vitamin E from gestation day 7 throughout lactation. Weight changes in the brain, hippocampus and cerebellum, DNA damage, and Hcy levels in the plasma, hippocampus, and cerebellum of male offspring were measured at the end of lactation. Results: The results revealed that along with a significant decrease in brain, cerebellum, and hippocampus weights in animals that received alcohol, the levels of DNA damage and Hcy significantly increased. Significant amelioration of brain atrophy and DNA damage as well as restoration of the elevated level of Hcy to that of controls were found in vitamin E-treated rats. Conclusions: These findings strongly support the idea that ethanol intake by dams during pregnancy and lactation induces Hcy-mediated oxidative stress in the developing hippocampus and cerebellum of offspring rats, and that these effects can be alleviated by vitamin E as an antioxidant. © 2009 by the Research Society on Alcoholism.