Cytotoxicity of 3-hydroxykynurenine in a neuronal hybrid cell line

The toxicity of 3-hydroxykynurenine (3HK), an endogenous tryptophan metabolite which is markedly elevated in rat CNS tissue as a result of neonatal vitamin B-6 deficiency, was investigated in a neuronally derived hybrid cell line (N18-RE-105). At concentrations in excess of 100 microM, 3HK was toxic to greater than 85% of cultured cells over the course of 24 h. The time course of 3HK toxicity was studied in cultures exposed to 500 microM 3HK. Cell lysis proceeded linearly to completion in 8-12 h, but the toxic effects of exposure for 2 h were irreversible. 3HK was the most potently toxic among several related kynurenine metabolites tested. The toxic effects of 3HK exposure were markedly attenuated or abolished in the presence of either catalase or glutathione, indicating, a role of oxidative stress in 3HK toxicity.