Nitric Oxide (No), Citrulline - No Cycle Enzymes, Glutamine Synthetase and Oxidative Stress in Anoxia (Hypobaric Hypoxia) and Reperfusion in Rat Brain

Abstract

Nitric oxide is postulated to be involved in the pathophysiology of neurological disorders due to hypoxia/ anoxia in brain due to increased release of glutamate and activation of N-methyl-D-aspartate receptors. Reactive oxygen species have been implicated in pathophysiology of many neurological disorders and in brain function. To understand their role in anoxia (hypobaric hypoxia) and reperfusion (reoxygenation), the nitric oxide synthase, argininosuccinate synthetase, argininosuccinate lyase, glutamine synthetase and arginase activities along with the concentration of nitrate /nitrite, thiobarbituric acid reactive substances and total antioxidant status were estimated in cerebral cortex, cerebellum and brain stem of rats subjected to anoxia and reperfusion. The results of this study clearly demonstrated the increased production of nitric oxide by increased activity of nitric oxide synthase. The increased activities of argininosuccinate synthetase and argininosuccinate lyase suggest the increased and effective recycling of citrulline to arginine in anoxia, making nitric oxide production more effective and contributing to its toxic effects. The decreased activity of glutamine synthetase may favor the prolonged availability of glutamic acid causing excitotoxicity leading to neuronal damage in anoxia. The increased formation of thiobarbituric acid reactive substances and decreased total antioxidant status indicate the presence of oxidative stress in anoxia and reperfusion. The increased arginase and sustained decrease of GS activity in reperfusion group likely to be protective.

Critical Evaluation of the Changes in Glutamine Synthetase Activity in Models of Cerebral Stroke

“…These researchers induced hypoxia by exposing rats to 8 % O 2 for 3 h, which led to an approximate 20 % reduction of glutamine synthetase specific activity in the striatum, cortex, and hippocampus [63] (Table 1), the regions most affected by stroke. Swamy et al [64] also reported an approximate 30 % loss of cortical glutamine synthetase specific activity following 5 min of anoxia (Table 1). In both of these studies, the cause for the reductions of specific activity was not ascertained.…”

“…In contrast to the situation with Á NO, EPR studies indicate significant hydroxyl radial production during the ischemia produced in the rat four-vessel occlusion model [71] and this production may account for the decrements of glutamine synthetase activity during cerebral oxygen starvation reported by Krajnc et al [63] and Swamy et al [64]. This hypothesis, however, remains to be confirmed.…”

“…The amounts of glutamine were determined by specific activity measurements (reported as activity in the table), electron microscopy (EM), Western blotting (WB), and immunohistochemistry (IMH). No change, increases or decreases are indicated by blue, green and red lettering, respectively a References Neurochem Res reperfusion [63,64,[72][73][74][75][76][77][78][79][80][81][82] (Table 1). These changes occurred notwithstanding the production of both the Á NO and hydroxyl radicals as measured directly by EPR [67,68] and indirectly by other measures [64,73,75,76,[78][79][80][81].…”

“…No change, increases or decreases are indicated by blue, green and red lettering, respectively a References Neurochem Res reperfusion [63,64,[72][73][74][75][76][77][78][79][80][81][82] (Table 1). These changes occurred notwithstanding the production of both the Á NO and hydroxyl radicals as measured directly by EPR [67,68] and indirectly by other measures [64,73,75,76,[78][79][80][81]. The initial rise in Á NO is probably due to the displacement of this molecule from cytochrome c oxidase, while the later elevation is due to the activation of Á NO synthase by the increases in cytosolic calcium elicited by glutamate acting via the NMDA and AMPA receptors [83][84][85][86][87].…”

The Effects ofPortulaca oleraceaon Hypoxia-Induced Pulmonary Edema in Mice

“…Five flavonoids were found in EEPO by capillary electrophoresis and electrochemical detection methods (Xu et al, 2006). Hypoxia can increase the ROS in mitochondria, which is the major material of oxidative stress (Swamy et al, 2010). Rahman (2003) hypoxia may result in an imbalance between antioxidant and pro-oxidant levels, which may aggravate lung inflammation.…”