Effect of oryzanol on transient middle cerebral artery occlusion induced ischemic stroke in atherosclerotic rats

Abstract

Aim and Objectives: Stroke (a cerebral vascular accident) the sudden death of brain cells as a result of inadequate blood supply. Atherosclerosis is the major risk factor for development of stroke and Oryzanol (a ferulic acid ester) has hypocholesterolemic and antioxidant effect. The aim of the present study is to evaluate effect of oryzanol on transient middle cerebral artery occlusion (tMCAO) induced ischemic stroke in Atherosclerotic rats and find out the possible mechanism lying beneath the effect. Materials and Methods: Sprague Dawley rats of either sex were used and divided in to five groups: Normal Control group, Atherosclerotic Control group, Atherosclerotic Sham operated group, Atherosclerotic cerebral ischemic group ,Oryzanol (100 mg/kg, p.o.) treated Atherosclerotic cerebral ischemic group. Atherosclerosis was induced by providing high fat diet (20% ground nut oil, 0.5% cholesterol, 1% cholic acid) for 32 days. The treatment with the oryzanol was started from the first day of treatment with high fat diet for 32 days. Serum biochemical parameters i.e. total cholesterol, triglyceride, LDL, HDL and VLDL were measured. On 33rd day, cerebral ischemia was induced by tMCAO. Oryzanol treatment was continued after the induction of ischemia from 34th day to 40th day. Neurological score was measured after on day 1 to day 7 at the interval of 24 hrs. Blood was collected, serum LDH level and CRP level were measured and animals were sacrificed and brain was excised. Brain damage indicator parameters like infarct volume, weight difference of brain hemisphere, nitrite level, Na+K+ATPase activity, lipid peroxidation, reduced glutathione level and SOD activity were measured. Results: After providing high fat diet there was significant increase in total cholesterol, Triglyceride LDL, VLDL level and decrease in HDL level in both Atherosclerosis group (322.1±24.60, 240±13.88, 39.63±3.67, 48.01±2.7 and 22.50±3.02 respectively) and Atherosclerosis Ischemic group (396.3±39.12, 225.9±13.44, 41.90±3.42, 45.17±2.6 and 18.86±3.09 respectively) as compared to the normal group (82.55±6.965, 82.14±19.24, 14.32±1.56, 16.43±3.8 and 33.60±1.49 respectively). After tMCAO surgery in Atherosclerotic rats caused significant increase in CRP(33.60±1.49), LDH(2302±100.4), MDA(5.128±0.53), nitrite (24.79±0.87) level and decrease in glutathione(2.567±0.47), superoxide dismutase (1.043±0.31) and Na+k+atpase activity (9.42±0.57) when compared to the normal group(2.187±0.66, 1112±28.53, 2.442±0.24, 10.10±1.15, 6.637±0.15, 4.686±0.20 and 20.80±1.26 respectively) Oryzanol (100 mg/kg, p.o.) treated animals showed significant reduction in total cholesterol(142±31.53), triglyceride(128.1±12.54),LDL(21.67±1.21),VLDL(25.62±2.5) in both Atherosclerosis and Atherosclerosis Ischemic animals. Oryzanol has shown significant decrease in CRP(3.09±0.34),LDH(1187±68.82),MDA(2.867±0.23) and nitrite level(16.16±0.53); and significant increase in glutathione(5.710±0.15) , superoxide dismutase(2.302±0.28) and Na+K+ATPase(16.77±1.27) activity in Atherosclerosis animals. After tMCAO brain hemisphere weight difference, brain infarct volume and neurological score was increased which is reduced by the Oryzanol treatment. Conclusion: Oryzanol has shown potent antihyperlipidmic activity in atherosclerotic animals.Oryzanol has also shown protective effect towards brain injury in tMCAO induced ischemic stroke in Atherosclerotic rats.