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Nonclinical Toxicology 13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility Valproate was administered orally to rats and mice at doses of 80 and 170 mg/kg/day (less than the maximum recommended human dose on a mg/m2 basis) for two years

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The deficiency of free CoA limits the efficiency of the Krebs cycle in activating anaerobic glucose metabolism (which inhibits pyruvate dehydrogenase activity, which is responsible for the conversion of pyruvate to acetyl-CoA in aerobic glucose metabolism in cells of the human organism), causing an increase in the concentration of toxic lactate in tissues [58,78,79]

doi: 10.1016/j.mce.2011.08.008 8 HaradaNHanadaKMinamiYKitakazeTOgataYTokumotoHet al