Oxidative stress as a mechanism of valproic acid-associated hepatotoxicity

Drug Metab Rev. 2006;38(4):627-39. doi: 10.1080/03602530600959433.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticonvulsants / toxicity*
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Chemical and Drug Induced Liver Injury / pathology
  • DNA / chemistry
  • DNA / drug effects
  • DNA / metabolism
  • Humans
  • Lipid Peroxidation / drug effects
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Reactive Oxygen Species / metabolism
  • Valproic Acid / toxicity*


  • Anticonvulsants
  • Reactive Oxygen Species
  • Valproic Acid
  • DNA