Fluorinated analogs as mechanistic probes in valproic acid hepatotoxicity: hepatic microvesicular steatosis and glutathione status

…, AG Borel, T Fujimiya, FS Abbott

Index: Tang; Borel; Fujimiya; Abbott Chemical Research in Toxicology, 1995 , vol. 8, # 5 p. 671 - 682

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Citation Number: 83

Abstract

It is postulated that the hepatotoxicity of valproic acid (VPA) results from the mitochondrial B- oxidation of its cytochrome P450 metabolite, 2-propyl-Cpentenoic acid (4-ene VPA), to 2- propyl-(E)-2, 4-pentadienoic acid ((E)-2, 4-diene VPA) which, in the CoA thioester form, either depletes GSH or produces a putative inhibitor of B-oxidation enzymes. In order td test this hypothesis, 2-fluoro-2-propyl-4-pentenoic acid (a-fluoro-4-ene VPA) which was ...