Effects of α-ketoglutarate on antioxidants and lipid peroxidation products in rats treated with sodium valproate

Abstract

Oxidative stress may cause free radical reactions to produce deleterious modifications in membranes, proteins, enzymes and DNA. Valproic acid is a major anti-epileptic drug with a broad spectrum of anti-epileptic activity. Chronic treatment with valproic acid can lead to elevated serum ammonia levels and specific oxidative metabolites of valproic acid have been associated with the drug's toxicity. The influence of sodium valproate treatment on lipid peroxidation and lipid profiles and the detoxifying effects of α-ketoglutarate on sodium valproate induced toxicity were studied in rats. The levels of thiobarbituric acid reactive substances, hydroperoxides and lipid profile variables (cholesterol, phospholipids, triglycerides and free fatty acids) were significantly increased in sodium valproate treated rats. Further, non-enzymic antioxidants (reduced glutathione) and the activities of the enzymic (superoxide dismutase, catalase, glutathione peroxidase) antioxidants were significantly decreased in sodium valproate treated rats. The levels were observed to be normal in α-KG + sodium valproate treated rats. These biochemical alterations during α-KG treatment could be due to (i) its ubiquitous collection of amino groups in body tissues, (ii) the participation of α-KG in non-enzymatic oxidative decarboxylation of the hydrogen peroxide decomposition process and (iii) its role in the metabolism of fats which could suppress oxygen radical generation and thus prevent lipid peroxidative damage.