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- Title
ROLE OF CITRULLINE-NITRIC OXIDE CYCLE ENZYMES AND ARGINASE IN KAINIC ACID MEDIATED EXCITOTOXICITY.
- Authors
Swamy, M.; Sirajudeen, K. N .S.; Govindasamy, Chandran
- Abstract
Introduction: Nitric oxide (NO) is known to be involved in the pathophysiology of many epilepsy models resulting from increased action of excitatory neurotransmitter namely glutamate. NO is synthesized from arginine by nitric oxide synthase (NOS) via the citrulline-NO cycle. Generation of NO is intertwined with the synthesis, catabolism and transport of arginine which thus ultimately participates in the regulation of normal and pathophysiological consequences of NO production. In order to understand the functional role of NO and citrulline-nitric oxide cycle enzymes in excitotoxicity, AS, AL and NOS activities along with arginase activity were analyzed in cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of rats subjected to excitotoxicity by kainic acid. Methodology: Excitotoxicity in rats was produced by subcutaneous administration of kainic acid (15mg/kg body weight, dissolved in normal saline) and control rats received normal saline. The animals were sacrificed after 2 hours of injection and brain regions (CC, CB and BS) were separated and homogenized. In the homogenates, the activities of NOS, AS and AL were assayed by colorimetric methods. Statistical analysis of results was done by using independent student t-test. Results: The activity of NOS was increased significantly (p<0.001 in CC, CB and p<0.01 in BS) and AL activity also showed an increase (p<0.001 in CB and p<0.01 in CC,BS) in excitotoxicity. AS activity was significantly increased (p<0.001) and no significant change observed in arginase activity of CC, CB and BS in kainic acid mediated excitotoxicity. Conclusions: The increased activity of NOS in this study support the formation of high amounts of NO in kainic acid mediated excitotoxicity. The increased activities of AS and AL indicate the effective supply of arginine for NO formation by NOS. The results of arginase indicate that there was no increased breakdown of arginine to ornithine and urea in the brain regions in this condition.
- Publication
Malaysian Journal of Medical Sciences, 2007, Vol 14, p177
- ISSN
1394-195X
- Publication type
Academic Journal