LONG-TERM ETHANOL ADMINISTRATION ENHANCES AGE-DEPENDENT MODULATION OFREDOX STATE IN CENTRAL AND PERIPHERAL ORGANS OF RAT - PROTECTION BY METADOXINE

Evidence is accumulating that intermediates of oxygen reduction may be associated with the development of alcoholic disease. In addition, fr ee radical-induced perturbation of the oxidant/antioxidant balance in cells is widely recognized as the main causative factor of age-related disorders. In the present work, we investigated the effects of 25 mon ths of ethanol consumption on the antioxidant defense system in differ ent organs of rat in comparison with normal aging, in the absence and presence of treatment with metadoxine, an ion pair composed of pirroli done carboxylate and pyridoxine. We demonstrate that aged rats underwe nt a significant perturbation of the antioxidant defense system, as in dicated by depletion of reduced glutathione (GSH) content, and increas es in oxidized GSH and free radical-induced luminescence associated wi th a decrease of GSH reductase and an increase of GSH transferase acti vities. These modifications, observed particularly in the liver and br ain with respect to other organs, were enhanced by long-term alcohol e xposure, and interestingly, significantly reduced after metadoxine sup plementation. Our results indicate that increased GSH transferase acti vity and decreased GSH reductase activity, followed by thiol depletion , are important factors sustaining a pathogenic role for oxidative str ess in aging and in all situations where age-correlated changes occur. Administration of metadoxine greatly reduces these metabolic abnormal ities. This evidence supports the pharmacological potential of metadox ine in the management of alcoholic disturbances.