Cocaine-induced liver injury in mice is mediated by nitric oxide and reactive oxygen species

Eur J Pharmacol. 1997 Oct 1;336(1):43-9. doi: 10.1016/s0014-2999(97)01230-2.


The modulating effects of nitric oxide (NO) and reactive oxygen species on cocaine-induced hepatotoxicity were examined by measuring plasma alanine aminotransferase activity and by carrying out histological studies. Liver injury was induced by a single injection of cocaine in adult male ICR mice. Pretreatment with aminoguanidine (an inhibitor of NO synthase), N-methyl-D-glucamine dithiocarbamate complex with iron ion (II) (Fe2+(MGD)2, a trapping reagent of NO) or deferoxamine complex with iron ion (III) (Fe3+-deferoxamine, a scavenger of NO) produced a marked inhibition of the hepatotoxicity induced by cocaine. In addition, pretreatment with allopurinol (an inhibitor of xanthine oxidase) and 1,3-dimethylthiourea (a scavenger of hydroxyl radical) also produced a potent inhibition. These findings suggest that a hydroxyl radical produced by the reaction of NO and superoxide anion (O2-) via peroxynitrite may be involved in the pathogenesis of cocaine hepatotoxicity.

Publication types

  • Comparative Study

MeSH terms

  • Allopurinol / therapeutic use
  • Animals
  • Antioxidants / therapeutic use
  • Chemical and Drug Induced Liver Injury*
  • Cocaine / toxicity*
  • Enzyme Inhibitors / therapeutic use
  • Guanidines / therapeutic use
  • Liver / drug effects
  • Liver / pathology
  • Liver Diseases / physiopathology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Reactive Oxygen Species / physiology*


  • Antioxidants
  • Enzyme Inhibitors
  • Guanidines
  • Reactive Oxygen Species
  • Nitric Oxide
  • Allopurinol
  • Nitric Oxide Synthase
  • Cocaine
  • pimagedine