الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
HC is a prevalent risk factor for the progression of atherosclerosis and is closely related to vascular disease that is considered as a major cause of morbidity and mortality throughout the world. This study aimed to establish a model of HC in rabbits and to detect the potential protective effect of imatinib and canagliflozin (CANA) against HC-induced atherosclerosis progression, vascular dysfunction, and hepatic damage. HCD was used to induce HC. NZW rabbits were fed 1% HCD for 4 weeks and imatinib (10 mg/kg/day) and CANA (10 mg/kg/day) were given orally from the first week. At the end of the experiment, blood samples were collected from marginal ear vein and serum was used for biochemical measurements. The aortas and liver were removed for homogenates preparation, measuring antioxidant status, estimation of vascular reactivity, and histopathological examination. HC exhibited significant elevations in serum lipid parameters, CRP, ALT, AST and ALP. Additionally, HC induced significant increases for aortic and hepatic MDA, aortic NO and hepatic PDGFR-β, while significantly exhibited reductions in aortic and hepatic GSH, SOD and hepatic PPARγ1. Moreover, HC produced impairment in ACh-enhanced aortic relaxation and aortic pathological changes. Histopathological examination of HC-fed rabbits revealed hepatic steatosis compared with non-treated group. Daily treatment with imatinib and CANA for 4 weeks significantly improved HCD-induced changes in lipid profile, revealed by reductions in serum levels of TC, TGs, LDL-C and increasing in HDL-C. Additionally, imatinib and CANA administration exhibited significant decreases in serum CRP. Furthermore, imatinib and CANA can improve liver function by decreasing serum ALT, AST, ALP. Moreover, imatinib and CANA induced significant decreases for aortic and hepatic MDA, aortic NO and hepatic PDGFR-β, while significantly exhibited elevations in aortic and hepatic GSH, SOD and hepatic PPARγ1 compared with HC animals. Furthermore, imatinib and CANA significantly protected against HC produced attenuation in ACh-induced aortic relaxation and pathological changes in aortic and hepatic tissues.