title: Oxidative mechanisms involved in kainate-induced cytotoxicity in cortical neurons.
abstract: In our previous experiments, evidence of free radical formation has been demonstrated in gerbil brain after kainic acid (KA) administration. In the present study, the mechanisms involved in KA-induced free radical formation and subsequent cell degeneration were investigated using high density cortical neuron cultures. A free radical trapping agent, alpha-phenyl-N-tert- butyl-nitrone (PBN), as well as the combined action of superoxide dismutase and catalase attenuated KA neurotoxic effect. Calpain-induced xanthine oxidase (XO) activation may play an important role in KA excitotoxicity since calpain inhibitor I as well as allopurinol, a selective XO inhibitor, significantly protected the cortical neurons from KA-induced cell death. However, XO activation may not be the only source producing free radicals, other free radical generating systems such as nitric oxide synthase may also play a role in KA insult.
authors.affiliation: Department of Pharmacology, University of Missouri-Columbia School of Medicine 65212.
authors.forename: Y
authors.initials: Y
authors.lastname: Cheng
authors.forename: A Y
authors.initials: AY
authors.lastname: Sun
mesh_terms: D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002154:Calpain / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D003497:Cyclic N-Oxides; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D016166:Free Radical Scavengers; D005609:Free Radicals; D006023:Glycoproteins / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000494:pharmacology; D010084:Oxidation-Reduction; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D006023:Glycoproteins; D009589:Nitrogen Oxides; C039304:calpain inhibitors; C029217:phenyl-N-tert-butylnitrone; D000493:Allopurinol; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D002154:Calpain; D007608:Kainic Acid