3-Hydroxykynurenine toxicity on the rat striatum in vivo.
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.
Nakagami
Y
Y
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Saito
H
H
Katsuki
H
H
D000111:Acetylcysteine / Q000627:therapeutic use; D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced* / Q000517:prevention & control; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D016166:Free Radical Scavengers / Q000627:therapeutic use; D007276:Injections, Intraventricular; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D016166:Free Radical Scavengers; C005045:3-hydroxykynurenine; D007737:Kynurenine; D017378:Quinolinic Acid; D000111:Acetylcysteine