AUDA as a modulator of lipid profile and endothelial function in diet induced hypercholesterolemia in rats

K. Ragab, Lubna Bayoumi, S. Nassar, Amany Abdelbary, Ola Barghash
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Abstract

Background: Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic acid produced by the vascular endothelium and act as important regulators of vascular tone. Objectives: to study the effect of soluble epoxide hydrolase inhibition AUDA on endothelial function in hypercholesterolemic rats. Methods: Hypercholesterolemia was induced by using Matos diet for 8 weeks and it significantly increased TC, TG, and LDL-C and decreased HDL-C. AUDA, was used with a dose of 0.35 mg/ kg for 10 weeks via gastric gavage every other day. Results: AUDA treated group has significantly lower total-C, TG, LDL-C and higher HDL-C as compared to untreated group. AUDA also improved vascular reactivity and vasodilatory response to different doses of Acetyl choline. Histopathological examination of aortic rings showed reduced development of atherosclerotic changes in the vascular wall with no effect on e-NOS expression in vascular endothelial cells. Conclusions: We can conclude that AUDA treatment has improved lipid profile and protect against development of atherosclerotic histopathological changes.
AUDA对饮食性高胆固醇血症大鼠脂质谱和内皮功能的调节作用
背景:环氧二碳三烯酸(EETs)是由血管内皮产生的花生四烯酸的细胞色素P450代谢物,是血管张力的重要调节因子。目的:研究可溶性环氧化物水解酶抑制剂AUDA对高胆固醇血症大鼠内皮功能的影响。方法:采用Matos饮食8周诱导高胆固醇血症,显著升高TC、TG、LDL-C,降低HDL-C。AUDA,每隔一天灌胃,剂量0.35 mg/ kg,连续10周。结果:与未治疗组相比,AUDA治疗组总c、TG、LDL-C明显降低,HDL-C明显升高。不同剂量乙酰胆碱也能改善血管反应性和血管舒张反应。主动脉环的组织病理学检查显示,血管壁动脉粥样硬化改变的发展减少,血管内皮细胞中e-NOS的表达未受影响。结论:我们可以得出结论,AUDA治疗可以改善血脂水平,防止动脉粥样硬化组织病理改变的发生。
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