الفهرس | Only 14 pages are availabe for public view |
Abstract Hypercholesterolemia is a dominant risk factor for the development of atherosclerosis and is closely related to vascular disease that is considered as a major cause of morbidity and mortality throughout the world. The modern lifestyle of high-cholesterol diet (HCD) and inadequate physical activity contributes to hypercholesterolemia, which increases the incidence of vascular disease. This study aimed to establish a model of hypercholesterolemia in rabbits and to explore the potential protective effect of dimethyl fumarate (DMF) and cinnamaldehyde (CIN) against hypercholesterolemia-induced vascular dysfunction. In the present study, HCD was used to induce hypercholesterolemia. NZW rabbits were fed 1% HCD for 4 weeks and DMF (12.5 mg/kg/day) and CIN (10 mg/kg/day) were given orally from the first week. At the end of the experiment, blood samples were collected and serum was used for biochemical measurements. The aortas were removed for homogenate preparation, measuring antioxidant status, estimation of vascular reactivity, real-time reverse transcriptase polymerase chain reaction (RT-PCR) and histopathological examination. HCD significantly increased triglycerides (TGs), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) levels. Moreover, HCD significantly upregulated mRNA expression of cholesteryl ester transfer protein (CETP) and myeloperoxidase (MPO). Additionally, HCD significantly decreased antioxidant enzyme activities and nitric oxide (NO) levels. Aortic relaxation to acetylcholine (ACh) was impaired and histopathological evaluation showed atherosclerosis. Daily treatment with CIN and DMF for 4 weeks significantly improved HCD-induced changes in lipid profile. The endothelial-dependent relaxation was also improved and aortic NO levels were ameliorated by DMF and CIN treatment. Moreover, DMF and CIN decreased MDA level, while increased CAT and SOD. Furthermore, they attenuated HCD-induced aortic structural. |