Effect of Oryzanol on Transient Middle Cerebral Artery Occlusion Induced Ischemic Stroke in Type-1 Diabetic Rates

Abstract

Aim and Objectives: Stroke is an acute focal neurological deficit which is the result of disturbance in the cerebral blood circulation. Stroke is third leading cause of death worldwide. Many studies report that hyperglycaemia worsens cerebral ischemic condition through enhancing ROS generation and subsequent neuronal injury. Several reports indicate that oryzanol has free radical scavenging, anti-inflammatory and blood glucose lowering effect. The study is aimed to evaluate effect of oryzanol on transient middle cerebral artery occlusion (tMCAO) induced ischemic stroke in type-1 diabetic rats. Materials and Methods: Wistar rats of either sex were used and divided in to eight groups: Normal control, diabetes control, diabetes sham operated, cerebral ischemic control (IR control), diabetes cerebral ischemic control (diabetic IR control), oryzanol (50 mg/kg, p.o.) treatment in diabetic IR animals (Diabetic IR O-50), oryzanol (100 mg/kg, p.o.) treatment in diabetic IR animals (Diabetic IR O-100), vitamin-E (100 mg/kg, p.o.) treatment in diabetic IR animals (Diabetic IR vita-E). Diabetes in rats was induced by streptozotocin (45 mg/kg, i.v.). The treatment with all test drug was started after induction of diabetes for 28 days. On 28th day, cerebral ischemia was induced by tMCAO using 4-0 intraluminal filament coated with poly-l-lysine and after 72 hours of the surgery blood was collected and animals were sacrificed. Various parameters like infarct volume, neurological score, weight difference of brain hemisphere, blood glucose, plasma LDH activity, nitrite level, Na+K+ATPase activity, lipid peroxidation, reduced glutathione level, catalase and SOD activity were measured. Results: Oryzanol (100 mg/kg, p.o.) treated animals showed significant reduction in infarct volumes, weight difference of brain hemisphere, neurological deficit, nitric oxide levels, lipid peroxidation, blood glucose level and plasma LDH activity with significant increase in Na+K+ATPase activity and antioxidant enzymes activity compared to diabetic IR control animals. Oryzanol (50 mg/kg/day, p.o.) treated animals showed reduced nitrite level, infarct volume, blood glucose level and plasma LDH activity with increased catalase and SOD activity compared to diabetic IR control animals.Vitamin-E treated animals showed significant reduction in blood glucose level, LDH activity, nitric oxide levels and lipid peroxidation with increased catalase and reduced glutathione. Conclusion: Oryzanol (100 mg/kg, p.o.) treatment reduced infarct volume, weight difference of brain hemisphere, neurological deficit and plasma LDH activity and thereby shows protective effect towards brain injury in tMCAO induced ischemic stroke. The possible mechanism of action of oryzanol might be blood glucose lowering effect, enhanced Na+K+ATPase activity and reduction in oxidative stress.