Effect of Oryzanol and Formulation-X on atherothrombotic risk factors in poloxamer-407 induced hyperlipidemia in mice

Abstract

AIM AND OBJECTIVES Atherothrombosis, a primary cause of cardiovascular disease (CVD) is a complex disease in which deposition of lipids, cholesterols as well as inflammation, and thrombus formation occurs in blood vessels. Gamma-oryzanol (OZ) has been reported for its lipid lowering potential. The present study was undertaken to evaluate the effect of OZ on atherothrombotic risk factors in poloxamer-407 induced hyperlipidemia in mice and find out possible mechanism of action. MATERIAL AND METHODS Swiss albino mice of either sex, weighing 35-40 g were divided randomly in 5 different groups: Normal control (NC), Poloxamer-407 treated (P-407), P-407 + OZ, Formulation- X (FOR-X) treated and Atorvastatin (ATOR) treated. Each group contains 6 animals. OZ (175mg/kg/day, p.o.), FOR-X (175mg/kg/day, p.o.) and ATOR (2mg/kg/day with 5% CMC, p.o.) were administered for 3 days. Hyperlipidemia was induced in mice with poloxamer-407 (30% w/w in distilled cool water, 500mg/kg, i.p.) on 3rd day of treatment. After 24 hrs of poloxamer-407 administration, animals were sacrificed. FeCl2 (50%) was used to induce right carotid artery thrombosis. Blood was collected and livers were isolated. Effect on various parameters like body weight, lipid profile, oxidative stress, coagulation time (APTT and PT) and thrombosis were assessed. RESULTS Treatment with OZ, FOR-X and ATOR improved lipid profile. They showed significant decrease in triglyceride, LDL-C, VLDL-C levels and significant increase in HDL-C level. OZ, FOR-X and ATOR treatments significantly reduced oxidative stress by decreasing lipid peroxidation, and restoration of antioxidant enzyme levels in liver homogenate as compared to poloxamer-407 group. Activated partial thromboplastine time and prothrombine time both were prolonged significantly by OZ, FOR-X and ATOR treatment as well as reduced endothelial cell damage in FeCl2 induced thrombosis in right carotid arteries.