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

Keywords: α-ketoglutarate , sodium valproate , antioxidants , lipid peroxidation

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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 antiepilepticactivity. Chronic treatment with valproic acid can lead to elevated serum ammonia levels andspecific oxidative metabolites of valproic acid have been associated with the drug’s toxicity. Theinfluence of sodium valproate treatment on lipid peroxidation and lipid profiles and the detoxifyingeffects of α-ketoglutarate on sodium valproate induced toxicity were studied in rats. The levels ofthiobarbituric acid reactive substances, hydroperoxides and lipid profile variables (cholesterol,phospholipids, triglycerides and free fatty acids) were significantly increased in sodium valproate treatedrats. Further, non-enzymic antioxidants (reduced glutathione) and the activities of the enzymic(superoxide dismutase, catalase, glutathione peroxidase) antioxidants were significantly decreased insodium valproate treated rats. The levels were observed to be normal in α-KG + sodium valproate treatedrats. These biochemical alterations during α-KG treatment could be due to (i) its ubiquitous collection ofamino groups in body tissues, (ii) the participation of α-KG in non-enzymatic oxidative decarboxylationof the hydrogen peroxide decomposition process and (iii) its role in the metabolism of fats which couldsuppress oxygen radical generation and thus prevent lipid peroxidative damage.


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