Effect of the Inhibition of Hydrogen Sulfide Synthesis on Ischemic Injury and Oxidative Stress Biomarkers in a Transient Model of Focal Cerebral Ischemia in Rats

Abstract

Hydrogen sulfide (H2S) plays multiple roles in the function of the central nervous system in physiological and pathological conditions, such as cerebral ischemia. Recent studies have reported controversial results about the role of H2S in cerebral ischemia. The aim of this study was to evaluate the effects of amino-oxyacetic acid (AOAA), an inhibitor of H2S synthesis, on ischemic injury in an experimental model of stroke. Using laser Doppler monitoring, cerebral ischemia was induced by transient middle cerebral artery occlusion (MCAO) for 1 hour in rats. AOAA (.025, .05, .1, and .5 mmol/kg intraperitoneally [i.p.]) was injected at the beginning of MCAO. Infarct volume, cerebral edema, and activity of antioxidant enzymes were measured using the standard methods 24 hours after ischemia. The administration of AOAA at doses .025, .05, and .1 mmol/kg significantly reduced the infarct volume (P < .001). Furthermore, .025 and .05 mmol/kg of AOAA significantly reduced brain edema and improved the neurological outcome (P < .001). The administration of AOAA did not significantly change the malondialdehyde content, activities of superoxide dismutase, or glutathione peroxidase antioxidant enzymes in the brain tissue (P > .05). The results showed that AOAA administered at a low dose has protective effects; however, at higher doses it did not exert any protective effect against cerebral ischemia and even worsened the ischemic injury. This finding suggests that H2S might be both beneficial and harmful in cerebral ischemic injury depending on its concentration in transient model of focal cerebral ischemia.