Protective Effect of Thymoquinone against Nephrotoxicity Induced by Cadmium in Rats
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.
[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.
[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.
@article{"International Journal of Biological, Life and Agricultural Sciences:72062", author = "Amr A. Fouad and Hamed A. Alwadaani and Iyad Jresat", title = "Protective Effect of Thymoquinone against Nephrotoxicity Induced by Cadmium in Rats", 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.", volume = "10", number = "2", pages = "73-4", }
