Yasuhiro Nakagami, Hiroshi Saito and Hiroshi Katsuki (*)
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan (*) To whom correspondence should be addressed.
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.
Keywords:
3-Hydroxykynurenine, Quinolinic acid, Huntington's disease