Enhancement of circulatory antioxidants by alpha-ketoglutarate during sodium valproate treatment in Wistar rats.

The effects of alpha-ketoglutarate (alpha-KG) on sodium valproate-induced hyperammonemia and hepatotoxicity were studied in biochemical experiments in rats. The levels of ammonia, urea, serum transaminases, hydroperoxides and thiobarbituric acid reactive substances were significantly increased in sodium valproate-treated rats. These levels were significantly decreased in alpha-KG- and sodium valproate-treated rats. Further, non-enzymatic (vitamins C and E) and enzymatic (superoxide dismutase and catalase) antioxidants were significantly decreased in sodium valproate-treated rats and were increased in alpha-KG- and sodium valproate-treated rats. These biochemical alterations during alpha-KG treatment could be due to (i) its ability to act as an ubiquitous collector of amino groups in body tissues, (ii) the participation of alpha-KG in the non-enzymatic oxidative decarboxylation in the hydrogen peroxide decomposition process and (iii) enhancing the proper metabolism of fats which could suppress oxygen radical generation and, thus, prevent the lipid peroxidative damages in rats.