Protective Effect of Thymoquinone against Nephrotoxicity Induced by Cadmium in Rats

Authors: Amr A. Fouad, Hamed A. Alwadaani, Iyad Jresat

Abstract:

The present study investigated the protective effect of thymoquinone (TQ), against cadmium-induced kidney injury in rats. Cadmium chloride (1.2 mg Cd/kg/day, s.c.), was given for nine weeks. TQ treatment (40 mg/kg/day, p.o.) started on the same day of cadmium administration and continued for nine weeks. TQ significantly decreased serum creatinine, renal malondialdehyde and nitric oxide, and significantly increased renal reduced glutathione in rats received cadmium. Histopathological examination showed that TQ markedly minimized renal tissue damage induced by cadmium. Immunohistochemical analysis revealed that TQ markedly decreased the cadmium-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, and caspase-3 in renal tissue. It was concluded that TQ significantly protected against cadmium nephrotoxicity in rats, through its antioxidant, antiinflammatory, and antiapoptotic actions.

Keywords: Thymoquinone, cadmium, kidney, rats.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1327254

References:

[1] M. Waisberg, P. Joseph, B. Hale, D. Beyersmann, “Molecular and cellular mechanisms of cadmium carcinogenesis,” Toxicology, vol. 192, pp. 95-117, 2003.
[2] S. Satarug, M.R. Moore, “Adverse health effects of chronic exposure to low-level cadmium in foodstuffs and cigarette smoke,” Environ. Health Perspect., vol. 112, pp. 1099-1103, 2004.
[3] F. Thevenod, “Nephrotoxicity and the proximal tubules. Insights from cadmium,” Nephron Physiol., vol. 93, pp. 87-93, 2003.
[4] P. Manna, M. Sinha, P.C. Sil, “Taurine plays a beneficial role against cadmium-induced oxidative renal dysfunction,” Amino Acids, vol. 36:pp. 417-428, 2009.
[5] J. Renugadevi, S.M. Prabu, “Quercetin protects against oxidative stressrelated renal dysfunction by cadmium in rats” Exp. Toxicol. Pathol., vol. 62, pp. 471-481, 2010.
[6] S. Darakhshan, A. Bidmeshki Pour, A. Hosseinzadeh Colagar, S. Sisakhtnezhad, “Thymoquinone and its therapeutic potentials,” Pharmacol. Res., vol. 95-96C, pp. 138-158, 2015.
[7] S. Samarghandian, M. Azimi-Nezhad, H. Mehrad-Majd, S.R. Mirhafez, “Thymoquinone ameliorates acute renal failure in gentamicin-treated adult male rats,” Pharmacology, vol. 96, pp. 112-117, 2015.
[8] M.M. Farag, G.O. Ahmed, R.R. Shehata, A.H. Kazem, “Thymoquinone improves the kidney and liver changes induced by chronic cyclosporine A treatment and acute renal ischaemia/reperfusion in rats,” J. Pharm. Pharmacol., vol. 67, pp. 731-739, 2015.
[9] F. Basarslan, N. Yilmaz, S. Ates, T. Ozgur, M. Tutanc, V.K. Motor, V. Arica, C. Yilmaz, M. Inci, S. Buyukbas, “Protective effects of thymoquinone on vancomycin-induced nephrotoxicity in rats,” Hum. Exp. Toxicol., vol. 31, pp. 726-733, 2012.
[10] I.O. Aycan, O. Tokgöz, A. Tüfek, U. Alabalık, O. Evliyaoğlu, H. Turgut, F. Çelik, A. Güzel, “The use of thymoquinone in nephrotoxicity related to acetaminophen,” Int. J. Surg., vol. 13:pp. 33-37, 2015.
[11] A.S. Awad, R. Kamel, M.A. Sherief, “Effect of thymoquinone on hepatorenal dysfunction and alteration of CYP3A1 and spermidine/spermine N-1-acetyl-transferase gene expression induced by renal ischaemia-reperfusion in rats,” J. Pharm. Pharmacol., vol. 63, pp. 1037-1042, 2011.
[12] O.M. Omran, “Effects of thymoquinone on STZ-induced diabetic nephropathy: an immunohistochemical study,” Ultrastruct. Pathol., vol. 38, pp. 26-33, 2014.
[13] A.I. Morales, C. Vicente-Sánchez, M. Jerkic, J.M. Santiago, P.D. Sánchez-González, F. Pérez-Barriocanal, J.M. López-Novoa, “Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats,” Toxicol. Appl. Pharmacol., vol. 210, pp. 128- 135, 2006.
[14] L. Pari, C. Sankaranarayanan, “Beneficial effects of thymoquinone on hepatic key enzymes in streptozotocin-nicotinamide induced diabetic rats,” Life Sci., vol. 85, pp. 830-834, 2009.
[15] A.A. Fouad, H.A. Qureshi, A.I. Al-Sultan, M.T. Yacoubi, A.A. Ali, “Protective effect of hemin against cadmium-induced testicular damage in rats,” Toxicology, vol. 257, pp. 153-160, 2009.
[16] Jr. S.M. Morris, T.R. Billiar, “New insights into the regulation of inducible nitric oxide synthesis,” Am. J. Physiol., vol. 266, pp. E829- E839, 1994.
[17] R.M. Clancy, S.B. Abramson, “Nitric oxide: a novel mediator of inflammation,” Proc. Soc. Exp. Biol. Med., vol. 210, pp. 93-101, 1995.
[18] A. El-Mahmoudy, H. Matsuyama, M.A. Borgan, Y. Shimizu, M.G. El- Sayed, N. Minamoto, T. Takewaki, “Thymoquinone suppresses expression of inducible nitric oxide synthase in rat macrophages,” Int. Immunopharmacol., vol. 2, pp. 1603-1611, 2002.
[19] J.K. Kundu, L. Liu, J.W. Shin, Y.J. Surh, “Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo,” Biochem. Biophys. Res. Commun., vol. 438, pp. 721-727, 2013.
[20] A.A. Fouad, I. Jresat, “Thymoquinone therapy abrogates toxic effect of cadmium on rat testes,” Andrologia, vol. 47, pp. 417-426, 2015.