Zofenopril down regulates inflammatory biomarkers and ameliorates atherosclerosis in hyperlipidemic male rabbits

The objective of this study is to assess the effects of Zofenopril on atherosclerosis via interfering with inflammatory and oxidative pathways. Twenty four local domestic rabbits were assigned to three groups (eight rabbits in each group): Group I is the control; group II, rabbit fed 1% cholesterol-diet (induced untreated group) and group III, 1% cholesterol-diet + zofenopril (0.5 mg/kg daily orally). Blood samples were collected at baseline, after 6 and after 12 weeks on experimental diets for measurement of serum lipids, serum high sensitive C-Reactive Protein (hsCRP) , serum interleukin-6 (IL-6) and tumor necrotic factor-alpha (TNF-a). Histopathological and histomorphometrical examination of the aorta was done at the end of 12 weeks to assess the atherosclerotic changes and aortic intima-media thickness respectively. Aortic malondialdehyde (MDA) and reduced glutathione (GSH) was also measured. Results showed a significant improvement in the levels of lipid parameters, atherogenic index in group III compared to group II at (P < 0.05). Zofenopril counteract the change in hsCRP, IL-6, TNF-a, GSH and MDA in compare with induced untreated group (P < 0.05). Morphologic analysis revealed that zofenopril markedly reduced (P< 0.05) the severity of atherosclerotic lesion in the aorta compared with rabbits on a high-fat diet alone and decreased aortic intima-media thickness in histomorphometric measurements. In conclusion, the current study illustrates the protective role of zofenopril against atherosclerosis progression in hypercholesterolemic rabbit via inhibition of inflammatory andoxidative pathways.