Nabila E. Abdelmeguid
Department of Zoology, Faculty of Science, Alexandria University, Moharram Bey, Alexandria 2151, Egypt
Hania N. Chmaisse
Faculty of Pharmacy, Beirut Arab University, Lebanon
Noura S. Abou Zeinab
Department of Biological and Environmental Sciences, Faculty of Sciesnce, Beirut Arab University, Lebanon
ABSTRACT
Cisplatin (CDDP) is a potent anticancer agents used for the treatment of solid tumors. However, its clinical use is often limited by its adverse effects including nephrotoxicity. The present study was designed to estimate if silymarin, a bioflavonoid with antioxidant potential can inhibit or at least ameliorate the alteration in some renal structures induced by cisplatin in rats or not. Five equal-sized groups (18 rats each) of male Sprague Dawley rats [Control, vehicle; cisplatin (5 mg/kg); silymarin (50 mg/kg) 2 h after cisplatin injection; and silymarin (50 mg/kg) 2 h before cisplatin injection] were used. Results revealed that cisplatin produced animal behavioral and morphological changes, as well as cellular and subcellular changes in kidneys. The most important changes were: decreased body weight, increased kidney wet weight, atrophied glomeruli, dilated urinary space, loss of PCT brush borders, hypertrophied podocyte pedicels, thickened glomerular basement membrane as well as tubular cell vacuolization. Post-treatment of silymarin 2 h after cisplatin however, significantly increase the body weight returning it to normal value, yet it failed in complete protection against the pathological alteration caused by cisplatin. Pre-treatment with silymarin 2 h before cisplatin significantly decreased the histological and ultrastructural changes induced by cisplatin and appear highly protective. These results suggested that the effects of cisplatin on glomerular and renal tubular cells morphology could be totally or to a great extent inhibited by silymarin.
PDF References
How to cite this article
Nabila E. Abdelmeguid, Hania N. Chmaisse and Noura S. Abou Zeinab, 2010. Protective Effect of Silymarin on Cisplatin-induced Nephrotoxicity in Rats. Pakistan Journal of Nutrition, 9: 624-636.
DOI: 10.3923/pjn.2010.624.636
URL: https://scialert.net/abstract/?doi=pjn.2010.624.636
DOI: 10.3923/pjn.2010.624.636
URL: https://scialert.net/abstract/?doi=pjn.2010.624.636
REFERENCES
- Ajith, T.A., N. Jose and K.K. Janardhanan, 2002. Amelioration of cisplatin induced nephrotoxicity in mice by ethyl acetate extract of a polypore fungus, Phellinus rimosus. J. Exp. Clin. Cancer Res., 21: 213-217.
PubMed - Arany, I. and R.L. Safirstein, 2003. Cisplatin nephrotoxicity. Semin. Nephrol., 23: 460-464.
CrossRefPubMedDirect Link - Behling, E.B., M.C. Sendao, H.D. Francescato, L.M. Antunes, R.S. Costa and L. Bianchi-Mde, 2006. Comparative study of multiple dosage of quercetin against cisplatin-induced nephrotoxicity and oxidative stress in rat kidneys. Pharmacol. Rep., 58: 526-532.
PubMedDirect Link - Borsari, M., C. Gabbi, F. Ghelfi, R. Grandi, M. Saladini, S. Severi and F. Borella, 2001. Silybin, a new iron-chelating agent. J. Inorganic Biochem., 85: 123-129.
CrossRefPubMedDirect Link - Chirino, Y.I., R. Hernandez-Pando and J. Pedraza-Chaveri, 2004. Peroxynitrite decomposition catalyst ameliorates renal damage and protein nitration in cisplatin-induced nephrotoxicity in rats. 1. BMC. Pharmacol., 4: 20-29.
CrossRef - Daugaard, G., U. Abilgaard, N.H. Holstein-Rathlou, I. Bruunshuus, D. Bucher and P.P. Leyssac, 1988. Renal tubular function in patients treated with high-dose cisplatin. Clin. Pharmacol. Ther., 44: 164-172.
PubMed - Daugaard, G., N.H. Holstein-Rathloum and P.P. Leyssac, 1988. Effect of cisplatin on proximal convuluted and straight segments of the rat kidney. J. Pharmacol. Exp. Ther., 244: 1081-1085.
Direct Link - El-Abd, S. and Y. Okda, 2007. Ameliorative role of silymarin against ribavarin induced toxicity in the kidney of albino rat. J. Exp. Biol. Zool., 3: 127-133.
Direct Link - Eminzade, S., F. Uras and F.V. Izzettin, 2008. Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals. Nutr. Metab., Vol. 5.
CrossRef - Gaedeke, J., L.M. Fels, C. Bokemeyer, U. Mengs, H. Stolte and H. Lentzen, 1996. Cisplatin nephrotoxicity and protection by silibinin. Nephrol. Dial. Transplant., 11: 55-62.
PubMedDirect Link - Hannemann, J. and K. Baumann, 1988. Ciplatin-induced lipid peroxidation and decrease of gluconeogenesis in rat kidney cortex: Different effects of antioxidants and radical scavengers. Toxicology, 51: 119-132.
PubMed - Hogan, F.S., N.K. Krishnegowda, M. Mikhailova and M.S. Kahlenberg, 2007. Flavonoid, silibinin, inhibits proliferation and promotes cell-cycle arrest of human colon cancer. J. Surg. Res., 143: 58-65.
PubMed - Ikarashi, Y., T. Kakyhara, C. Imai, A. Tanaka, A. Watanabe and M. Uchyyama, 2004. Glomerular dysfunction, independent of tubular dysfunction, induced by antineoplastic chemotherapy in children. Pediatr. Int., 46: 570-575.
PubMed - Kakihara, T., C. Imai, H. Hotta, Y. Ikarashi, A. Tanaka and M. Uchiyama, 2003. Impaired tubular excretory function as a late renal side effect of chemotherapy in children. J. Pediatr. Hematol. Oncol., 25: 209-214.
PubMed - Karimi, G., M. Ramezani and Z. Tahoonian, 2005. Cisplatin nephrotoxicity and protection by milk thistle extract in rats. Evid Based Comp. Alt. Med., 2: 383-386.
Direct Link - Kohn, S., M. Fradis, J. Ben-David, J. Zidan and E. Robinson, 2002. Nephrotoxicity of combined treatment with cisplatin and gentamicin in the guinea pig: Glomerular injury findings. Ultrastruct. Pathol., 26: 371-382.
PubMed - Kuhlmann, M.K., E. Horsch, G. Burkhardt, M. Wagner and H. Kohler, 1998. Reduction of cisplatin toxicity in cultured renal tubular cells by the bioflavonoid quercetin. Arch. Toxicol., 72: 536-540.
PubMed - Laekeman, G., S. De Coster and K. De Meyer, 2003. St. Marys Thistle: An overview. J. Pharm. Belg., 58: 28-31.
PubMed - L'Azou, B., I. Dubus, C. Ohayon-Courtes and J. Cambar, 2007. Human glomerular mesangial IP15 cell line as a suitable model for in vitro cadmium cytotoxicity studies. Cell Biol. Toxicol., 23: 267-278.
PubMed - Lee, C.K., K.K. Park, S.S. Lim, J.H. Park and W.Y. Chung, 2007. Effects of the licorice extract against tumor growth and cisplatin-induced toxicity in a mouse xenograft model of colon cancer. Biol. Pharm. Bull., 30: 2191-2195.
PubMedDirect Link - Loh, A.H.L. and A.H. Cohen, 2009. Drug-induced kidney disease-pathology and current concepts. Ann. Acad. Med. Singapore, 38: 240-250.
PubMed - Mansour, H.H., H.F. Hafez and N.M. Fahmy, 2006. Silymarin modulates Cisplatin-induced oxidative stress and hepatotoxicity in rats. J. Biochem. Mol. Biol., 39: 656-661.
PubMedDirect Link - Matsushima, H., K. Yonemura, K. Ohishi and A. Hishida, 1998. The role of oxygen free radicals in cisplatin-induced acute renal failure in rats. J. Lab. Clin. Med., 131: 518-526.
PubMed - Montine, T.J. and R.F. Borch, 1990. Role of endogenous sulfur containing nucleophiles in an in vitro model of cis-diamminedichloroplatinium-induced nephrotoxicity. Biochem. Pharmacol., 39: 1751-1757.
Direct Link - Mora, L.de.O., L.M.G. Antunes, H.D.C. Francescato and M.de.L.P. Bianchi, 2003. The effects of oral glutamine on cisplatin-induced nephrotoxicity in rats. Pharmacol. Res., 47: 517-522.
CrossRefPubMedDirect Link - Morales, A.I., C. Vicente-Sanchez, J.M.S. Sandoval, J. Egido and P. Mayoral et al., 2006. Protective effect of quercetin on experimental chronic cadmium nephrotoxicity in rats is based on its antioxidant properties. Food Chem. Toxicol., 44: 2092-2100.
CrossRefPubMedDirect Link - Morigi, M., K. Imberti, C. Zoja, D. Corna and S. Tomasoni, 2004. Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute renal failure. J. Am. Soc. Nephrol., 15: 1794-1804.
PubMed - Pal, S., A.S. Sadhu, S. Patra and K.K. Mukherjea, 2008. Histological vis-a-vis biochemical assessment on the toxic level and antineoplastic efficacy of a synthetic drug Pt-ATP on experimental animal models. J. Exp. Clin. Cancer Res., 27: 68-68.
PubMed - Park, H.R., E.J. Ju, S.K. Jo, U. Jung, S.H. Kim and S.T. Yee, 2009. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice. BMC Cancer, 9: 85-85.
PubMed - Pratibha, R., R. Sameer, P.V. Rataboli, D.A. Bhiwgade and C.Y. Dhume, 2006. Enzymatic studies of Cisplatin 10 mg kg-1 platin induced oxidative stress in hepatic tissue of rats. Eur. J. Pharmacol., 532: 290-293.
PubMed - Rao, M. and M.N. Rao, 1998. Protective effects of selenomethionine against cisplatin-induced renal toxicity in mice and rats. J. Pharm. Pharmacol., 50: 687-691.
PubMed - Rodriguez-Barbero, A., B. L'Azou, J. Cambar and J.M. Lopez-Novoa, 2000. Potential use of isolated glomeruli and cultured mesangial cells as in vitro models to assess nephrotoxicity. Cell Biol. Toxicol., 16: 145-153.
PubMed - Saad, S.Y., T.A.O. Najjar and M. Alashari, 2004. Role of non-selective adenosine receptor blockade and phosphodiesterase inhibition in cisplatin-induced nephrogonadal toxicity in rats. Clin. Exp. Pharmacol. Physiol., 31: 862-867.
CrossRefPubMedDirect Link - Sadzuka, Y., T. Shoij and A. Takino, 1992. Effects of cisplatin on the activity of enzymes which protect against lipid peroxidation. Biochem. Pharmacol., 43: 1872-1875.
PubMed - Shalaby, T., A.M. Ghanem and H.S. Ramadan, 2006. Cytotoxicity changes of cisplatin drug in the presence of magnetic fields. Romanian J. Biophys., 4: 229-241.
Direct Link - Shimeda, Y., Y. Hirotani, Y. Akimoto, K. Shindou, Y. Ijiri, T. Nishihori and K. Tanaka, 2005. Protective effects of capsaicin against cisplatin-induced nephrotoxicity in rats. Biol. Pharm. Bull., 28: 1635-1638.
Direct Link - Stewart, D.J., R.S. Benjamin, M. Luna, L. Feun, R. Caprioli, W. Seifert and T.L. Loo, 1982. Human tissue distribution of platinum after cis-diamminedichloroplatinum. Cancer Chemother. Pharmacol., 10: 51-54.
CrossRef - Yilmaz, H.R., M. Iraz, S. Sogut, H. Ozyurt, Z. Yildirim, O. Akyol and S. Gergerlioglu, 2004. The effects of erdosteine on the activities of some metabolic enzymes during cisplatin-induced nephrotoxicity in rats. Pharmacol. Res., 50: 287-290.
PubMed