Carbon tetrachloride-induced lipid peroxidation: eicosanoid formation and their regulation by antioxidant nutrients

Toxicology. 2003 Jul 15;189(1-2):113-27. doi: 10.1016/s0300-483x(03)00157-4.


Hepatic injury through carbon tetrachloride (CCl(4)) induced lipid peroxidation is well known and has been extensively used in the experimental models to understand the cellular mechanisms behind oxidative damage and further to evaluate the therapeutic potential of drugs and dietary antioxidants. Many of these methods that have often been used to study free-radical induced lipid peroxidation suffer methodological discrepancies when considering the measurements in vivo. Recent discovery of isoprostanes, non-enzymatically derived prostaglandin F(2)-like compounds, unfolded a new era of determination of oxidant stress in vivo. Cyclooxygenase (COX) catalysed prostaglandins formation from arachidonic acid and their involvement in inflammation is well known. This review mainly focuses on the formation of non-enzymatically and enzymatically catalysed eicosanoids, namely the isoprostanes and prostaglandin F(2alpha) (PGF(2alpha)), following CCl(4) treatment in animals and their regulation by antioxidants. Both eicosanoids are increased dramatically in the peripheral plasma, urine and/or liver tissues but with diverse kinetics of formation, release and excretion pattern. Free radical and COX-mediated oxidation of arachidonic acid products are intimately associated with experimental hepatotoxicity. Studies suggest that there is a link between initial involvement of oxidative stress and subsequent induction of the COX mediated inflammatory process, which may have an eminent role in the pathogenesis of liver diseases. Antioxidant nutrients have been shown to affect both the formation of isoprostanes and prostaglandin metabolite but the therapeutic values and exact mechanisms of action remain unclear.

Publication types

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

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Carbon Tetrachloride / adverse effects*
  • Carbon Tetrachloride / pharmacology
  • Chemical and Drug Induced Liver Injury
  • Cytochrome P-450 Enzyme System / metabolism
  • Dinoprost / biosynthesis*
  • Dinoprost / metabolism
  • Humans
  • Isoprostanes / biosynthesis*
  • Isoprostanes / metabolism
  • Lipid Peroxidation / drug effects
  • Lipid Peroxides / biosynthesis*
  • Lipid Peroxides / metabolism
  • Liver Diseases / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Reactive Oxygen Species / metabolism


  • Antioxidants
  • Isoprostanes
  • Lipid Peroxides
  • Reactive Oxygen Species
  • Cytochrome P-450 Enzyme System
  • Dinoprost
  • Carbon Tetrachloride
  • Prostaglandin-Endoperoxide Synthases