Nephrotoxicity is the main secondary effect of cyclosporine A (CsA) treatment. The antioxidant action of Nigella sativa oil (NSO) may explain the protective effect of these agents against various hepatotoxic and nephrotoxic models in vivo and in vitro. This study was designed to investigate the possible protective effects of NSO, in prevention of chronic CsA-induced nephrotoxicity in rats. Animals were randomly divided into four experimental groups: the control group received sunflower oil, the other groups were treated with CsA (25 mg/kg/day b.w. orally) or NSO (2 ml/kg orally) or CsA + NSO, respectively. Urine and serum creatinine levels, tissue superoxide dismutase, glutathione peroxidase and catalase enzyme activities, and nitric oxide and malondialdehyde levels were measured, and histological examination was performed. In our study, CsA caused a significant deterioration in the renal function, morphology and gave rise to severe oxidative stress in the kidney. NSO significantly improved the functional and histological parameters and attenuated the oxidative stress induced by CsA. In conclusion, our study demonstrated for the first time that NSO protects kidney tissue against oxygen free radicals, preventing renal dysfunction and morphological abnormalities associated with chronic CsA administration.

1.
Burits M, Bucar F: Antioxidant activity of Nigella sativa essential oil. Phytother Res 2000;14:323–328.
2.
Ali BH, Blunden G: Pharmacological and toxicological properties of Nigella sativa. Phytother Res 2003;17:299–305.
3.
El Daly ES: Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats. J Pharm Bel 1998;53:87–95.
4.
Badary OA, Nagi MN, Al-Shabanah OA, Al-Shawaf HA, Al-Sohaibani MO, Al-Bekairi AM: Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and potentiates its antitumor activity. Can J Physiol Pharmacol 1997;75:1356–1361.
5.
Ali BH: The effect of Nigella sativa oil on gentamicin nephrotoxicity in rats Am J Chin Med 2004;32:49–55.
6.
Cohen DJ, Loertscher R, Rubin MF, Tilney NL, Carpenter CB, Strom TB: Cyclosporine: a new immunosuppressive agent for organ transplantation. Ann Intern Med 1984;101:667–682.
7.
Andoh TF, Bennett WM: Chronic cyclosporine nephrotoxicity. Curr Opin Nephrol Hypertens 1998;7:265–270.
8.
Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–275.
9.
Sun Y, Oberley LW, Li Y: A simple method for clinical assay of superoxide dismutase. Clin Chem 1988;34:497–500.
10.
Aebi H: Catalase; in Bergmeyer HU (ed): Methods of Enzymatic Analysis. New York, Academic Press, 1974, pp 673–677.
11.
Paglia DE, Valentine WN: Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70:158–170.
12.
Esterbauer H, Cheeseman KH: Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal; in Packer L, Glazer AN (eds): Oxygen Radicals in Biological Systems. Methods in Enzymology. San Diego, Academic Press, 1990, pp 407–421.
13.
Cortas NK, Wakid NW: Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 1990;36:1440–1443.
14.
Li C, Yang CW, Kim WY, Jung JY, Cha JH, Kim YS, Kim J, Bennett WM, Bang BK: Reversibility of chronic cyclosporine nephropathy in rats after withdrawal of cyclosporine. Am J Physiol Renal Physiol 2003;284:389–398.
15.
Kang DH, Kim YG, Andoh TF, Gordon KL, Suga S, Mazzali M, Jefferson JA, Hughes J, Bennett W, Schreiner GF, Johnson RJ: Post-cyclosporine-mediated hypertension and nephropathy: Amelioration by vascular endothelial growth factor. Am J Physiol Renal Physiol 2001;280:727–736.
16.
Pichler RH, Franceschini N, Joung BA, Hugo C, Andoh TF, Burdmann EA, Shankland SJ, Alpers CE, Bennett WM, Couser WG: Pathogenesis of cyclosporine nephropathy: Roles of angiotensin II and osteopontin. J Am Soc Nephrol 1995;6:1186–1196.
17.
Walker RJ, Lazzaro VA, Duggin GG, Horvath JS, Tiller DJ: Evidence that alterations in renal metabolism and lipid peroxidation may contribute to cyclosporine nephrotoxicity. Transplantation 1990;50:487–492.
18.
Vardi N, Parlakpinar H, Ozturk F, Acet A: Gentamicin-induced nephrotoxicity and protective effect of caffeic acid phenethyl ester in rats. Fundam Clin Pharmacol 2005;19:173–177.
19.
Yildirim Z, Sogut S, Odaci E, Iraz M, Ozyurt H, Kotuk M, Akyol O: Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats. Pharmacol Res 2003;47:149–156.
20.
Ateşşahin A, Ceribaşı AO, Yılmaz S: Lycopene, a carotenoid, attenuates cyclosporine-induced renal dysfunction and oxidative stress in rats. Basic Clin Pharmacol Toxicol 2007;100:372–376.
21.
Parra T, De Arriba G, Arribas I, Perez de Lema G, Rodriguez-Puyol D, Rodriguez-Puyol M: Cyclosporine A nephrotoxicity: role of thromboxane and reactive oxygen species. J Lab Clin Med 1998;131:63–70.
22.
Mohamadin AM, El-Beshbishy HA, El-Mahdy MA: Green tea extract attenuates cyclosporine A-induced oxidative stress in rats. Pharmacol Res 2005;51:51–57.
23.
Durak I, Karabacak HI, Buyukkocak S, Cimen MY, Kacmaz M, Omeroglu E, Ozturk HS: Impaired antioxidant defense system in the kidney tissues from rabbits treated with cyclosporine. Protective effects of vitamins E and C. Nephron 1998;78:207–211.
24.
Sabry A, El-Husseini A, Sheashaa H, Abdel-Shafy E, El-Dahshan K, Abdel-Rahim M, Abdel-Kaleek E, Abo-Zena H: Colchicine vs. omega-3 fatty acids for prevention of chronic cyclosporine nephrotoxicity in Sprague-Dawley rats: an experimental animal model. Arch Med Res 2006;37:933–940.
25.
El Daly ES: Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats. J Pharm Bel 1998;53:87–95.
26.
Nagi MN, Alam K, Badary OA, al-Shabanah OA, al-Sawaf HA, al-Bekairi AM: Thymoquinone protects against carbon tetrachloride hepatotoxicity in mice via an antioxidant mechanism. Biochem Mol Biol Int 1999;47:153–159.
27.
Turkdogan MK, Agaoglu Z, Yener Z, Sekeroglu R, Akkan HA, Avci ME: The role of antioxidant vitamins (C and E), selenium and Nigella sativa in the prevention of liver fibrosis and cirrhosis in rabbits, new hopes. Dtsch Tierärztl Wochenschr 2000;108:71–73.
28.
Inselmann G, Hannemann J, Baumann K: Cyclosporine A induced lipid peroxidation and influence on glucose-6-phosphatase in rat hepatic and renal microsomes. Res Commun Chem Pathol Pharmacol 1990;68:189–203.
29.
Suleymanlar G, Suleymanlar I, Shapiro JI, Chan L: Possible role of lipid peroxidation in cyclosporine nephrotoxicity in rats. Transplant Proc 1994;26:2888–2889.
30.
Walker RJ, Lazzaro VA, Duggin GG, Horvath JS, Tiller DJ: Evidence that alterations in renal metabolism and lipid peroxidation may contribute to cyclosporine nephrotoxicity. Transplantation 1990;50:487–492.
31.
Bobadilla NA, Gamba G, Tapia E, Garcia-Torres R, Bolio A, Lopez-Zetina P, Herrera-Acosta J: Role of NO in cyclosporin nephrotoxicity: effects of chronic NO inhibition and NO synthases gene expression. Am J Physiol 1998;274:791–798.
32.
Mihatsch MJ, Kyo M, Morozumi K, Yamaguchi Y, Nickeleit V, Ryffel B: The side effects of cyclosporine A and tacrolimus. Clin Nephrol 1998;49:356–363.
33.
Mihatsch MJ, Ryffel B, Gudat F: The differential diagnosis between rejection and cyclosporine toxicity. Kidney Int Suppl 1995;63–69.
34.
Myers BD, Ross J, Newton L, Luetscher J, Perlroth M: Cyclosporine-associated chronic nephropathy. N Engl J Med 1984;311:699–705.
35.
Vieira JM Jr, Noronha IL, Malheiros DM, Burdmann EA: Cyclosporine-induced interstitial fibrosis and arteriolar TGF-beta expression with preserved renal blood flow. Transplantation 1999;68:1746–1753.
36.
Whiting PH, Thompson AW, Blair JT, Simpson JG: Experimental cyclosporin A nephrotoxicity. Br J Exp Pathol 1982;63:88–94.
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