Effects of acute ammonia toxicity on nitric oxide (NO), citrulline-NO cycle enzymes, arginase and related metabolites in different regions of rat brain.
Nitric oxide (NO) is involved in many pathophysiological processes in the brain. NO is synthesized from arginine by nitric oxide synthase (NOS) enzymes. Citrulline formed as a by-product of the NOS reaction, can be recycled to arginine by successive actions of argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) via the citrulline-NO cycle. Hyperammonemia is known to cause poorly understood perturbations of the citrulline-NO cycle. To understand the role of citrulline-NO cycle in hyperammonemia, NOS, ASS, ASL and arginase activities, as well as nitrate/nitrite (NOx), arginine, ornithine, citrulline, glutamine, glutamate and GABA were estimated in cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of rats subjected to acute ammonia toxicity. NOx concentration and NOS activity were found to increase in all the regions of brain in acute ammonia toxicity. The activities of ASS and ASL showed an increasing trend whereas the arginase was not changed. The results of this study clearly demonstrated the increased formation of NO, suggesting the involvement of NO in the pathophysiology of acute ammonia toxicity. The increased activities of ASS and ASL suggest the increased and effective recycling of citrulline to arginine in acute ammonia toxicity, making NO production more effective and contributing to its toxic effects.
Swamy
M
M
Department of Chemical Pathology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia. mswamy@kb.usm.my
Zakaria
Adlin Zafrulan
AZ
Govindasamy
Chandran
C
Sirajudeen
K N S
KN
Nadiger
H A
HA
D000596:Amino Acids / Q000187:drug effects / Q000378:metabolism; D000641:Ammonia / Q000633:toxicity*; D000818:Animals; D001119:Arginase / Q000187:drug effects* / Q000378:metabolism; D001123:Argininosuccinate Lyase / Q000187:drug effects / Q000378:metabolism; D001124:Argininosuccinate Synthase / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002956:Citrulline / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000187:drug effects / Q000378:metabolism
D000596:Amino Acids; D009566:Nitrates; D009573:Nitrites; D002956:Citrulline; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D000641:Ammonia; D019001:Nitric Oxide Synthase; D001119:Arginase; D001123:Argininosuccinate Lyase; D001124:Argininosuccinate Synthase