The Hepatotoxicity of Valproic Acid and Its Metabolites in Rats. I. Toxicologic, Biochemical and Histopathologic Studies
James W. Kesterson, G. Richard Granneman, Joseph M. Machinist – 1 November 1984 – Valproic acid (VPA), its unsaturated metabolites and pent‐4‐enoate (4‐PA) were studied for potential hepatotoxicity in rats. 4‐PA, 4‐en‐VPA and 2,4‐dien‐VPA were potent inducers of microvesicular steatosis in young rats. Microvesicular steatosis induced by the 4‐en‐VPA was accompanied by ultrastructural changes characterized by myeloid bodies, lipid vacuoles and mitochondrial abnormalities. Myeloid bodies and lipid vacuoles were seen to a lesser extent in 2,4‐dien‐VPA and 4‐PA‐treated rats.