4-chloro-3-hydroxyanthranilate attenuate quinolinic acid accumulation in brain following transient cerebral ischemia in the gerbil.

Abstract

The kynurenine pathway is the predominant route of L-tryptophan metabolism in most tissues. Two aspects of L-tryptophan catabolism through this pathway are of particular interest. Firstly, the initial enzyme of the kynurenine pathway in extrahepatic tissues, indoleamine-2,3-dioxygenase (IDO), is induced by interferon-y and other immune stimuli (Saito et al., 1991,1992; Takikawa et al., 1986). Such induction is observed in patients with cancer, infectious disease and following therapeutic interferon administration, and has been implicated in the anti-proliferative and anti-microbial effects of interferon-y (Yasui et al., 1986; Taylor et al., 1991). Secondly, the neuroactive nature of certain metabolites, including quinolinic acid (QUIN), an excitotoxic agonist of N-methyl-D-aspartate receptors, and kynurenic acid (KYNA) an antagonist of excitatory amino acid receptors, has implicated their involvement in a broad spectrum of neurodegenerative disease (Heyes et al., 1992,1993). In a previous study, accumulation of QUIN in gerbil brain was observed 4 and 7 days following transient cerebral ischemia (Saito et al., see Figure 1). Such increases have been demonstrated to be secondary to increases of IDO and other kynurenine pathway enzymes in infiltratedKeywordsQuinolinic AcidKynurenic AcidKynurenine PathwayCarotid Artery OcclusionTransient Cerebral IschemiaThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.