Antioxidant and Anti-Inflammatory Efficacy of Optimized Ezetimibe Chitosan Nanoparticles against the Induced- Hyperlipidemia in Rats
Middle East Journal of Applied Sciences · 2021
Hyperlipidemia not only involves an elevation in serum lipids, but it is also an inflammatory disease, as excessive lipid accumulation is known to trigger local inflammatory responses with the production of oxidative stress.The developed and optimized formula of ezetimibe chitosan nanoparticles encompassing 30 mg EZE together with low molecular weight of chitosan at a ratio to TPP 1.75: 2, showed a considerable superior anti-hyperlipidemia when compared to the marketed product.This study investigated the role of optimized ezetimibe chitosan nanoparticles (optimized formula) in combating the oxidative stress and inflammation against induced -hyperlipidemia in rats.forty male rats were divided into two main groups: normal control (10 rats) and hyperlipidemia group where hyperlipidemia rat model was created by oral administration of cholesterol -cholic acid mixture in a ratio of 3:1 and feeding on 55gm butter /kg diet for ten weeks, then this group divided into three subgroups; hyperlipidemia, ezetimibe treated group (0.9mg/kg b.wt) and optimized formula treated group (0.63mg/kg b.wt).Ezetimibe and optimized formula were prescribed for 4 weeks.Hyperlipidemia induced a significant increase in serum total cholesterol, triglycerides, aminotransferases (ALT and AST) in association with a significant decrease in serum total antioxidant capacity.Additionally , marked increase in malondialdehyde (MDA) level along with significant decline in reduced glutathione (GSH) content, antioxidant enzymes (glutathione S-transferase and Catalase) and nitric oxide (NO) production were observed in liver tissue of hyperlipidemia group.Hepatic tumor necrosis factor -alpha (TNF-α) was significantly increased in association with a significant decrease in interleukin 10 (IL-10).Treatment with Ezetimibe or the optimized formula effectively ameliorated these disorders and elicited their efficiency against oxidative stress and inflammation with the priority of the optimized formula.According to the obtained data, it can be concluded that treatment with optimized formula significantly relieved hyperlipidemia, by ameliorating the levels of aminotransferases with the suppression of oxidative stress and inflammation.