Nitric oxide (NO), citrulline-NO cycle enzymes, glutamine synthetase, and oxidative status in kainic acid-mediated excitotoxicity in rat brain.
Neuronal excitation, involving the excitatory glutamate receptors, is recognized as an important underlying mechanism in neurodegenerative disorders. To understand their role in excitotoxicity, the nitric oxide synthase (NOS), argininosuccinate synthetase (AS), argininosuccinate lyase (AL), glutamine synthetase (GS), and arginase activities, along with the concentration of nitrate/nitrite, thiobarbituric acid-reactive substances (TBARS), and total antioxidant status (TAS), were estimated in the cerebral cortex, cerebellum, and brain stem of rats subjected to kainic acid-mediated excitotoxicity. The results of this study clearly demonstrated the increased production of NO by increased activity of NOS. The increased activities of AS and AL suggest the increased and effective recycling of citrulline to arginine in excitotoxicity, making NO production more effective and contributing to its toxic effects. The decreased activity of GS may favor the prolonged availability of glutamic acid, causing excitotoxicity, leading to neuronal damage. The increased formation of TBARS and decreased TAS indicate the presence of oxidative stress in excitotoxicity.
Department of Chemical Pathology, School of Medical Sciences, University Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. mswamy@kb.usm.my
Mummedy
M
Swamy
Kuttulebbai N S
KN
Sirajudeen
Govindasamy
G
Chandran
D000818:Animals; D001224:Aspartic Acid; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002956:Citrulline / Q000378:metabolism*; D004730:Endothelium, Vascular; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D007608:Kainic Acid; D009126:Muscle Relaxation; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D002956:Citrulline; D001224:Aspartic Acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D005974:Glutamate-Ammonia Ligase; D007608:Kainic Acid