Effect of Simvastatin on Cisplatin-induced Nephrotoxicity in Male Rats Prevention of cisplatin-induced nephrotoxicity
Iranian Journal of Pharmaceutical Sciences,
Vol. 7 No. 3 (2011),
1 July 2011
,
Page 165-173
https://doi.org/10.22037/ijps.v7.41313
Abstract
Statins have antioxidant and anti-inflammatory effects that are not directly related to their cholesterol-lowering activity. This study aimed to investigate the effect of simvastatin on the extent of tissue damage in cisplatin-induced nephrotoxicity. Simvastatin was orally given to rats in different doses (1, 2 and 4 mg/kg), 1 h prior to cisplatin injection (5 mg/kg, i.p.). All animals were decapitated 5 days after cisplatin administration. Blood urea nitrogen, creatinine, K and Na levels were measured. The kidney samples used for the measurement of malondialdehyde and glutathione levels or were processed for histopathological studies. Simvastatin at 1 mg/kg caused a significant decrease in serum Na and a significant increase in serum K. Simvastatin at 2 mg/kg significantly increased serum Na, and at 4 mg/kg significantly prevented decrease of GSH levels by cisplatin and significantly decreased serum Na levels. The morphological changes induced by cisplatin treatment were prevented only by 4 mg/kg dose of simvastatin. Thus, simvastatin at 4 mg/kg dose is beneficial in cisplatin-induced nephrotoxicity in rats via prevention of lipid peroxidation, inflammation and endothelial function impairment.
Keywords:
- Cisplatin
- Nephrotoxicity;
- Oxidative stress;
- Simvastatin.
How to Cite
Mohammad Javad Khoshnoud, Baligh Naji Abdeh Moghbel, Hossein Niknahad, & Bita Geramizadeh. (2011). Effect of Simvastatin on Cisplatin-induced Nephrotoxicity in Male Rats: Prevention of cisplatin-induced nephrotoxicity. Iranian Journal of Pharmaceutical Sciences, 7(3), 165–173. https://doi.org/10.22037/ijps.v7.41313
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[2] Iseri S, Ercan F, Gedik N. Simvastatin attenuates cisplatin-induced kidney and liver damage in rats. Toxicol. 2007;230(2-3):256-64.
[3] Epstein M, Campese V. Pleiotropic effects of 3hydroxy-3-methylglutaryl coenzyme a reductase inhibitors on renal function. Am J kidney dis.2005;45(1):2-14.
[4] Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of cisplatin nephrotoxicity. Toxins. 2010;2(11):2490-518.
[5] Casarett L, Klaassen C, Doull J, editors. Casarett and Doull's toxicology: the basic science of poisons. New York: McGraw-Hill; 2008.
[6] Ali B, Al Moundhri M. Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compounds: a review of some recent research. Food Chem Toxicol. 2006;44(8):1173-83.
[7] Yi A, Xin H, Yan W, Zhou X. Amelioration of cisplatin-induced nephrotoxicity by pravastatin in mice. ExpToxicol Pathol. 2011;63:215-9.
[8] Owen JA, Iggo B, Scandert F, Stewart C. The determination of creatinine in plasma or serum, and in urine; a critical examination. Biochem J.1954 58(3):426.
[9] Hosten A, editor. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Boston Butterworths; 1990.
[10] Ekor M, Emerole G, Farombi E. Phenolic extract of soybean (Glycine max) attenuates cisplatininduced nephrotoxicity in rats. Food Chem Toxicol.2010;48(4):1005-12.
[11] Zwart d, Loeckie L, Meerman JH, Commandeur JN, Vermeulen NP. Biomarkers of free radical damage : Applications in experimental animals and in humans. Free Radical Biol Medicine.1999;26 (1-2):202-26.
[12] Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal biochem. 1979;95(2):351-8.
[13] Sedlak J, Lindsay R. Estimation of total, proteinbound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal biochem.1968;25(1):192.
[14] Sweetman S, Martindale W. The complete drug reference 35th ed. Martindale W, editor. London: Pharmaceutical Press; 2005.
[15] Launay-Vacher V, Rey J-B, Isnard-Bagnis C, Deray G, Daouphars M. Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Cancer Chemother Pharmacol. 2008;61:903-9.
[16] Hughes A, Stricklett P, Padilla E, Kohan D. Effect of reactive oxygen species on endothelin-1 production by human mesangial cells. Kidney Int. 1996;49(1):181-9.
[17] Lovari J, Mesic M, Macan M, Koprivanac M, Kelava M, Vlasta B. Measurement of malondialdehyde (MDA) level in rat plasma after simvastatin treatment using two different analytical methods. Perid Biol 2008;110(1):63-7.
[18] Francescato HsDC, Costa RS, Camargo SMR, Zanetti MA, Lavrador MA, Bianchi MdLP. Effect of oral selenium administration on cisplatininduced nephrotoxicity
in rats. Pharmacol Res. 2001;43(1):77-82.
[19] Saad A, Youssef M, El-Shennawy L. Cisplatininduced damage in kidney genomic DNA and nephrotoxicity in male rats: The protective effect of grape seed proanthocyanidin extract. Food Chem Toxicol. 2009;47(7):1499-506.
[20] Sueishi K, Mishima K, Makino K, Itoh Y, Tsuruya K, Hirakata H, et al. Protection by a radical scavenger edaravone against cisplatin-induced nephrotoxicity in rats. Eu J Pharmacol. 2002;451(2):203-8.
[21] Mittler R. Oxidative stress, antioxidants and stress tolerance. Trends Plant sci. 2002;7(9):405-10.
[22] Gutteridge J. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem. 1995;41(12):1819.
[23] Bagchi D, Garg A, Krohn R, Bagchi M, Bagchi D, Balmoori J, et al. Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice. Gen Pharmacol. 1998;30(5):771-6.
[24] Suzuki C, Cherian M. The interactions of cisdiamminedichloroplatinum with metallothionein and glutathione in rat liver and kidney. Toxicol.1990;64(2):113-27.
[25] Montine T, Borch R. Role of endogenous sulfurcontaining nucleophiles in an in vitro model of cis-diamminedichloroplatinum (II)-induced nephrotoxicity. Biochem Pharmacol. 1990;39(11):1751-7.
[26] Meyer K, Madias N. Cisplatin nephrotoxicity. Miner electrol metabol. 1994;20(4):201.
[27] Greggi Antunes L, Joana D'arc C, Bianchi MdLP.Protective effects of vitamin C aganist Cisplatininduced nephrotoxicity and lipid peroxidation in adult rats:A dose-
dependent study. Pharmacol Res. 2000;41(4):405-11.
[28] Schupp N, Schmid U, Heidland A, Stopper H.Rosuvastatin protects against oxidative stress and DNA damage in vitro via upregulation of glutathione synthesis. Atherosclerosis.2008;199(2):278-87.
[29] Athyros V, Mikhailidis D, Papageorgiou A, Symeonidis A, Pehlivanidis A, Bouloukos V, et al. The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study. J Clin Path.2004;57(7):728.
[30] Shepherd J, Kastelein JJP, Bittner V, Deedwania P, Breazna A, Dobson S, et al. Effect of intensive lipid lowering with atorvastatin on renal function in patients with coronary heart disease: the Treating to New Targets (TNT) study. Clin J Am Soc Neph. 2007;2(6):1131.
[31] Zhou M, Schuman I, Jaimes E, Raij L.Renoprotection by statins is linked to a decrease in renal oxidative stress, TGF- , and fibronectin with concomitant increase in nitric oxide bioavailability.Am J Physiol Renal Physiol.2008;295(1):F53.
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