3-Hydroxykynurenine toxicity on the rat striatum in vivo

Jpn J Pharmacol. 1996 Jun;71(2):183-6. doi: 10.1254/jjp.71.183.

Abstract

3-Hydroxykynurenine (3-HK) is a tryptophan metabolite whose level in the brain is elevated under several pathological states including Huntington's disease. In the present study, we examined the possible toxicity of 3-HK by injection of this substance into rat brain. Intrastriatal injection of 3-HK (50 nmol) induced tissue damage around the injected site. Quinolinic acid (QA) at 200 nmol also induced tissue damage, which was comparable in size to that induced by 50 nmol 3-HK. Co-administration of MK-801 significantly reduced QA-induced lesion, but failed to prevent 3-HK-induced lesion. On the other hand, the antioxidant N-acetyl-L-cysteine (10 nmol) reduced 3-HK-induced damage. Thus, 3-HK may be involved in brain pathogenesis by providing oxygen radicals.

Publication types

  • Comparative Study

MeSH terms

  • Acetylcysteine / therapeutic use
  • Animals
  • Brain Diseases / chemically induced*
  • Brain Diseases / prevention & control
  • Corpus Striatum / drug effects*
  • Corpus Striatum / pathology
  • Free Radical Scavengers / therapeutic use
  • Injections, Intraventricular
  • Kynurenine / analogs & derivatives*
  • Kynurenine / toxicity
  • Male
  • Quinolinic Acid / toxicity
  • Rats
  • Rats, Wistar

Substances

  • Free Radical Scavengers
  • 3-hydroxykynurenine
  • Kynurenine
  • Quinolinic Acid
  • Acetylcysteine