Cardioprotective Effects of Nigella sativa Oil on Cyclosporine A‐Induced Cardiotoxicity in Rats

Abstract

Cyclosporine A is a well-known immunosuppressor agent universally used in allotransplantation. However, it has been demonstrated that this drug produces side-effects in several organs, particularly in the kidney and in the heart. Nigella sativa oil has long been used in folk medicine for a wide range of illnesses. One of the potential properties of N. sativa oil is the ability of one or more of its constituents to reduce toxicity due to its antioxidant activities. The antioxidant effects of N. sativa oil have been examined using different hepatic and kidney toxicity in in vivo murine models. The aim of this study was to evaluate the effects of N. sativa oil in the antioxidant enzyme status and myocardium of cyclosporine-A-treated rats. This study included 24 male Wistar albino young healthy rats (8-12 weeks) weighing 150-200 g. The control group received sunflower oil (21 days, 2 ml/kg/day, orally) without any treatment. The second group received only N. sativa oil (21 days, 2 ml/kg, orally) (N. sativa oil group). The animals in the third group received only cyclosporine A (21 days, 25 mg/kg, orally) (cyclosporine A group). The animals in the fourth group were treated with cyclosporine A (21 days, 25 mg/kg, orally) and starting one day before cyclosporine A administration were treated with N. sativa oil (21 days, 2 ml/kg, orally) (cyclosporine A + N. sativa oil group). Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities in the heart tissues were significantly reduced in the cyclosporine A group compared to control values. Nigella sativa oil treatment caused an increase in the activities of SOD, CAT and GSH-Px compared to the control group. Malondialdehyde (MDA), nitric oxide and protein carbonyl (PC) levels were increased in the cyclosporine A-treated group in comparison with the control and N. sativa groups. Co-administration of N. sativa oil and cyclosporine A abrogated the cyclosporine A-induced MDA, N. sativa oil and PC increase compared to the cyclosporine A group. The results of our study show that pre-treatment with N. sativa oil reduced the subsequent cyclosporine A injury in rat heart, demonstrated by normalized cardiac histopathology, decrease in lipid peroxidation, improvement in antioxidant enzyme status and cellular protein oxidation. Cyclosporine A is the most frequently used immunosup-pressor agent in transplant surgery and in the treatment of autoimmune diseases, because of its specific inhibiting effect on the signal transduction pathways of the T cell receptor [1]. However, the major limiting factors for the clinical use of the drug are the adverse effects, which include nephrotoxicity [2], hypertension [3], hepatotoxicity [4] and cardiotoxicity [5,6]. Moreover, the use of cyclosporine A is also reported to be related to increased vasoconstriction and vascular endothelial dysfunction [7]. Although the mechanisms by which cyclosporine A-induced cardiotoxicity are still not clear and is a matter of debate, recent studies have reported that oxidative stress mi...

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