Oxidative stress is one of the major pathological mechanisms involved in cerebral ischemia and reperfusion injury. Diabetes is one of the major risk factor for cerebral ischemic stroke. Increased base line levels of oxidative stress in diabetes will lead to cerebral ischemic damage. In pathological conditions such as cerebral ischemia/reperfusion injury free radical production is more than their elimination through antioxidant defence mechanisms leading to increased injury of brain. Newer anti-diabetic drugs of the class DPP-4 inhibitors such as, vildagliptin and alogliptin was reported to have antioxidant properties apart from its antihyperglycemic activity. Therefore the aim of the present study was to evaluate the antioxidant effect of vildagliptin and alogliptin against cerebral infarction induced ischemia reperfusion injury in normal and STZ induced diabetic wistar rats. Cerebral infarction was induced by bilateral common carotid artery occlusion followed by 4 hr reperfusion. Percent infarction, oxidative stress markers such as malondialdehyde, superoxide dismutase and catalase and biochemical parameters such as glucose, LDH, SGOT and CK-BB were measured. Treatment with vildagliptin and alogliptin for a period of four weeks produced significant reduction in percent cerebral infarct volume. At vildagliptin dose 10 mg/kg dose there was a significant reduction in oxidative stress markers like MDA, LDH, SGOT and CK-BB in diabetic group when compared to normal group and in contrast significant increase in antioxidant markers like superoxide dismutase and catalase levels. Similar to vildagliptin, alogliptin at the dose of 30 mg/kg also showed significant reduction in oxidative stress markers like MDA, LDH, SGOT and CK-BB in diabetic group when compared to normal group and in contrast significant increase in antioxidant markers like superoxide dismutase and catalase levels. Vildagliptin and alogliptin showed significant cerebroprotective effect by antioxidant mechanisms.
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