The aim of the study was to determine whether a combination of pyridoxine and pyrrolidone carboxylate (PCA) could influence the antioxidant defence system in hepatic and extrahepatic tissues during acute ethanol administration. The results showed that ethanol treatment led to a significant depletion of reduced glutathione and increase in oxidized glutathione (GSSG) in the different organs, associated with decreased activity of glutathione reductase. Pretreatment of animals with Metadoxine (PCA + pyridoxine) one hour before ethanol administration produced a significant protection against glutathione (GSH) depletion in the different organs examined. This was consistent with an increase in glutathione reductase activity. In view of the fact that free thiol compounds such as glutathione are vital in cellular defence against oxidants and that decreases in reduced glutathione precede lethal cell injury resulting from free radical accumulation, our study supports the effectiveness of Metadoxine as a useful therapeutic agent effective in the management of all those pathological conditions where a severe imbalance of cellular redox state seems to take place as a result of the generation of free radical species.