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Abstract Thymoquinone, the main active ingredient of the volatile oil of N. sativa seed poses many beneficial anti-oxidant effects. Oxidative stress has been implicated in the pathogenesis of both atherosclerosis and CsA-induced toxicity; two factors that participate in the development of CAN. In this work we aim to study the therapeutic effects of TQ in minimizing atherogenesis and CsA-toxicity in the AHR model. A number of 36 New Zealand white female rabbits we divided into 5 groups; Group I, control; Group II, 1% cholesterol diet for 8 weeks; Group III, 1% cholesterol diet + TQ (10 mg/kg/day) for 8 weeks; Group IV, 1% cholesterol diet + CsA (25 mg/kg/day) for 8 weeks; Group V, 1% cholesterol diet + TQ (10 mg/kg/day) + CsA (25 mg/kg/day) for 8 weeks. Blood samples were collected after 8 weeks for measurement of serum lipids (TC, TG, LDL-C, HDL-C and TC/HDL-C ratio) and oxidative stress parameters (MDA and protein carbonyl). Liver, kidney and aortic tissue specimens was taken for assessment of tissue oxidative stress and toxic effects of TQ and/or CsA and aortic atherosclerosis. The high-cholesterol diet in group II increased the serum lipids, oxidative stress parameters and induced atherosclerosis and fatty liver. TQ and the high cholesterol diet in group III significantly reduced the oxidative stress parameters in serum and tissues and decreased the atherosclerosis by 40% and improved fatty liver. CsA and high-cholesterol diet in group IV increased serum, aortic and kidney oxidative stress parameters and atherosclerosis severity compared to Groups II. It also induced ischemic glomerular changes and interstitial fibrosis in the kidney tissues. TQ in group V, reduced aortic atherosclerosis by 52% compared to Group IV. It also minimized the CsA induced changes in the kidney. |