Protective Effects of Selenium on Cyclophosphamide-Induced Oxidative Stress and Kidney Injury
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Cyclophosphamide (CP) is a common anticancer drug, but its use in cancer treatment is limited due to its severe toxicities induced mainly by oxidative stress in normal cells. Reactive oxygen species (ROS) lead to multiple organ injuries, including the kidneys. Selenium (Se) is a nutritionally essential trace element with antioxidant properties. In the present study, the possible protective effect of Se on CP-induced acute nephrotoxicity was investigated. Forty-two Sprague-Dawley rats were equally divided into six groups of seven rats in each. The control group received saline, and other groups were injected with CP (150 mg/kg), Se (0.5 or 1 mg/kg), or CP + Se intraperitoneally. Total antioxidant capacity (TAC), total oxidant state (TOS), oxidative stress index (OSI), creatinine, and cystatin C (Cys C) levels were measured in the sera. In addition, kidney tissues were examined histologically. In the CP alone treated rats, creatinine, Cys C, TOS, and OSI levels increased, while TAC level decreased. CP-induced histological damages were decreased by co-treatment of Se and biochemical results supported the microscopic observations. In conclusion, our study points to the therapeutic potential of Se and indicates a significant role of ROS in CP-induced kidney toxicity.
KeywordsCyclophosphamide Oxidative stress Nephrotoxicity Selenium Creatinine Cystatin C
This work was supported by Eskisehir Osmangazi University Scientific Research Project Commission, Eskisehir, Turkey, with the project number 2014-254.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 8.Kaur R, Kaur K (2000) Effects of dietary selenium on morphology of testis and cauda epididymis in rats. Indian J Pharmacol 44(3):265–272Google Scholar
- 11.Wang F, Shu G, Peng X, Fang J, Chen K, Cui H, Chen Z, Zuo Z, Deng J, Geng Y, Lai W (2013) Protective effects of sodium selenite against aflatoxin B1-induced oxidative stress and apoptosis in broiler spleen. Int J Environ Res Public Health 10(7):2834–2844. https://doi.org/10.3390/ijerph10072834 CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Chen K, Shu G, Peng X, Fang J, Cui H, Chen J, Wang F, Chen Z, Zuo Z, Deng J, Geng Y, Lai W (2013) Protective role of sodium selenite on histopathological lesions, decreased T-cell subsets and increased apoptosis of thymus in broilers intoxicated with aflatoxin B(1). Food Chem Toxicol 59:446–454. https://doi.org/10.1016/j.fct.2013.06.032 CrossRefPubMedGoogle Scholar
- 16.Ognjanovic BI, Djordjevic NZ, Matic MM, Obradovic JM, Mladenovic JM, Stajn AS, Saicic ZS (2012) Lipid peroxidative damage on cisplatin exposure and alterations in antioxidant defense system in rat kidneys: a possible protective effect of selenium. Int J Mol Sci 13(2):1790–1803. https://doi.org/10.3390/ijms13021790 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Xia L, Yunlong Z, Yuan Y, Yong S, Yan Q, Zeyuan D, Hongyan L (2016) Protective effects of selenium, vitamin E, and purple carrot anthocyanins on d-galactose-induced oxidative damage in blood, liver, heart and kidney rats. Biol Trace Elem Res 173(2):433–442. https://doi.org/10.1007/s12011-016-0681-8 CrossRefGoogle Scholar
- 24.Sugumar E, Kanakasabapathy I, Abraham P (2007) Normal plasma creatinine level despite histological evidence of damage and increased oxidative stress in the kidneys of cyclophosphamide treated rats. Clin Chim Acta 376(1–2):244–245. https://doi.org/10.1016/j.cca.2006.04.006 CrossRefPubMedGoogle Scholar
- 25.Abraham P, Isaac B (2011) Ultrastructural changes in the rat kidney after single dose of cyclophosphamide-possible roles for peroxisome proliferation and lysosomal dysfunction in cyclophosphamide-induced renal damage. Hum Exp Toxicol 30(12):1924–1930. https://doi.org/10.1177/0960327111402240 CrossRefPubMedGoogle Scholar
- 28.Rehman MU, Tahir M, Ali F, Qamar W, Lateef A, Khan R, Quaiyoom A, Oday OH, Sultana S (2012) Cyclophosphamide-induced nephrotoxicity, genotoxicity, and damage in kidney genomic DNA of swiss albino mice: the protective effect of ellagic acid. Mol Cell Biochem 365(1–2):119–127. https://doi.org/10.1007/s11010-012-1250-x CrossRefPubMedGoogle Scholar
- 34.Carmen AP, Michael GS, Judd S, Cushman M, McClellan W, Zakai NA, Safford MM, Zhang X, Muntner P, Warnock D (2011) Detection of chronic kidney disease with creatinine, cystatin C, and urine albumin-to-creatinine ratio and association with progression to end-stage renal disease and mortality. JAMA 305(15):1545–1552. https://doi.org/10.1001/jama.2011.468 CrossRefGoogle Scholar
- 35.Macisaac RJ, Tsalamandris C, Thomas MC, Premaratne E, Panagiotopoulos S, Smith TJ, Poon A, Jenkins MA, Ratnaike SI, Power DA, Jerums G (2007) The accuracy of cystatin C and commonly used creatinine-based methods for detecting moderate and mild chronic kidney disease in diabetes. Diabet Med 24(4):443–448. https://doi.org/10.1111/j.1464-5491.2007.02112.x CrossRefPubMedGoogle Scholar
- 36.Ray S, Pandit B, Das S, Chakraborty S (2011) Cyclophosphamide-induced lipid peroxidation and changes in cholesterol content: protective role of reduced glutathione. IJPS 7(4):255–267Google Scholar