Oxidative Stress as a Mechanism of Valproic Acid-Associated Hepatotoxicity

Abstract

Valproic acid (2-n-propylpentanoic acid; VPA) has several therapeutic indications, but it is used primarily as an anticonvulsant. VPA is a relatively safe drug, but its use is associated with idiosyncratic hepatotoxicity, which in some cases may lead to fatality. The underlying mechanism responsible for the hepatotoxicity is still not well understood, but various hypotheses have been proposed, including oxidative stress. This article discusses the experimental evidence on the effect of VPA on the various indices of oxidative stress and on the potential role of oxidative stress in VPA-associated hepatotoxicity.

Key Words :

• α-Fluoro-valproic acid
• Hepatotoxicity
• Oxidative stress
• Reactive oxygen species
• Valproic acid.

Notes

*Presented at the Seventh International Symposium on Biological Reactive Intermediates, Tucson, Arizona, January 4–7, 2006.