Advertisement

Biological Trace Element Research

, Volume 185, Issue 1, pp 116–123 | Cite as

Protective Effects of Selenium on Cyclophosphamide-Induced Oxidative Stress and Kidney Injury

  • Sibel Gunes
  • Varol Sahinturk
  • Sema Uslu
  • Adnan Ayhanci
  • Sedat Kacar
  • Ruhi Uyar
Article
First Online:
Received:
Accepted:
  • 419 Downloads

Abstract

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.

Keywords

Cyclophosphamide Oxidative stress Nephrotoxicity Selenium Creatinine Cystatin C 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgements

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.

References

  1. 1.
    Sakthivel KM, Guruvayoorappan C (2015) Acacia ferruginea inhibits cyclophosphamide-induced immunosuppression and urotoxicity by modulating cytokines in mice. J Immunotoxicol 12(2):154–163.  https://doi.org/10.3109/1547691X.2014.914988 CrossRefPubMedGoogle Scholar
  2. 2.
    Olayinka E, Ore A, Ola O, Adeyemo O (2015) Ameliorative effect of gallic acid on cyclophosphamide-induced oxidative injury and hepatic dysfunction in rats. Med Sci 3(3):78–92.  https://doi.org/10.3390/medsci3030078 Google Scholar
  3. 3.
    Gunes S, Ayhanci A, Sahinturk V, Altay DU, Uyar R (2017) Carvacrol attenuates cyclophosphamide-induced oxidative stress in rat kidney. Can J Physiol Pharmacol 95(7):844–849.  https://doi.org/10.1139/cjpp-2016-0450 CrossRefPubMedGoogle Scholar
  4. 4.
    Haldar S, Dru C, Bhowmick NA (2014) Mechanisms of hemorrhagic cystitis. Am J Clin Exp Urol 2(3):199–208PubMedPubMedCentralGoogle Scholar
  5. 5.
    Kawanishi M, Matsuda T, Nakayama A, Takebe H, Matsui S, Yagi T (1998) Molecular analysis of mutations induced by acrolein in human fibroblast cells using supF shuttle vector plasmids. Mutat Res 417(2–3):65–73.  https://doi.org/10.1016/S1383-5718(98)00093-X CrossRefPubMedGoogle Scholar
  6. 6.
    Mythili Y, Sudharsan PT, Selvakumar E, Varalakshmi P (2004) Protective effect of DL-alpha-lipoic acid on cyclophosphamide induced oxidative cardiac injury. Chem Biol Interact 151(1):13–19.  https://doi.org/10.1016/j.cbi.2004.10.004 CrossRefPubMedGoogle Scholar
  7. 7.
    Agar G, Alpsoy L, Bozari S, Erturk FA, Yildirim N (2013) Determination of protective role of selenium against aflatoxin B1-induced DNA damage. Toxicol Ind Health 29(5):396–403.  https://doi.org/10.1177/0748233711434956 CrossRefPubMedGoogle Scholar
  8. 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
  9. 9.
    Abul-Hassan KS, Lehnert BE, Guant L, Walmsley R (2004) Abnormal DNA repair in selenium-treated human cells. Mutat Res 565(1):45–51.  https://doi.org/10.1016/j.mrgentox.2004.09.004 CrossRefPubMedGoogle Scholar
  10. 10.
    Li JL, Gao R, Li S, Wang JT, Tang ZX, Xu SW (2010) Testicular toxicity induced by dietary cadmium in cocks and ameliorative effect by selenium. Biometals 23(4):695–705.  https://doi.org/10.1007/s10534-010-9334-0 CrossRefPubMedGoogle Scholar
  11. 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. 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
  13. 13.
    Leibovitz B, Hu ML, Tappel AL (1990) Dietary supplements of vitamin E, beta-carotene, coenzyme Q10 and selenium protect tissues against lipid peroxidation in rat tissue slices. J Nutr 120(1):97–104CrossRefPubMedGoogle Scholar
  14. 14.
    Darvesh AS, Bishayee A (2010) Selenium in the prevention and treatment of hepatocellular carcinoma. Anti Cancer Agents Med Chem 10(4):338–345.  https://doi.org/10.2174/187152010791162252 CrossRefGoogle Scholar
  15. 15.
    Kaur P, Bansal MP (2005) Effect of selenium-induced oxidative stress on the cell kinetics in testis and reproductive ability of male mice. Nutrition 21(3):351–357.  https://doi.org/10.1016/j.nut.2004.05.028 CrossRefPubMedGoogle Scholar
  16. 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. 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
  18. 18.
    Hasanvand A, Abbaszadeh A, Darabi S, Nazari A, Gholami M, Kharazmkia A (2017) Evaluation of selenium on kidney function following ischemic injury in rats; protective effects and antioxidant activity. J Renal Inj Prev 6(2):93–98.  https://doi.org/10.15171/jrip.2017.18 CrossRefPubMedGoogle Scholar
  19. 19.
    Cao S, Durrani FA, Rustum YM (2004) Selective modulation of the therapeutic efficacy of anticancer drugs by selenium containing compounds against human tumor xenografts. Clin Cancer Res 10(7):2561–2569.  https://doi.org/10.1158/1078-0432.CCR-03-0268 CrossRefPubMedGoogle Scholar
  20. 20.
    Gunes S, Sahinturk V, Karasati P, Sahin IK, Ayhanci A (2017) Cardioprotective effect of selenium against cyclophosphamide-induced cardiotoxicity in rats. Biol Trace Elem Res 177(1):107–114.  https://doi.org/10.1007/s12011-016-0858-1 CrossRefPubMedGoogle Scholar
  21. 21.
    Erel O (2005) A new automated colorimetric method for measuring total oxidant status. Clin Biochem 38(12):1103–1111.  https://doi.org/10.1016/j.clinbiochem.2005.08.008 CrossRefPubMedGoogle Scholar
  22. 22.
    Aycicek A, Erel O, Kocyigit A (2005) Decreased total antioxidant capacity and increased oxidative stress in passive smoker infants and their mothers. Pediatr Int 47(6):635–639.  https://doi.org/10.1111/j.1442-200x.2005.02137.x CrossRefPubMedGoogle Scholar
  23. 23.
    Senthilkumar S, Devaki T, Manohar BM, Babu MS (2006) Effect of squalene on cyclophosphamide-induced toxicity. Clin Chim Acta 364(1–2):335–342.  https://doi.org/10.1016/j.cca.2005.07.032 CrossRefPubMedGoogle Scholar
  24. 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. 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
  26. 26.
    Abraham P, Isaac B (2016) Imbalance between peroxisomal ros generating enzymes and ROS scavenging enzymes may contribute to cyclophosphamide induced renal damage in rats. Biochemist 6(11):72–77.  https://doi.org/10.15373/2249555X Google Scholar
  27. 27.
    Qu T, Wang E, Li A, Du G, Li Z, Qin X (2016) NMR based metabolomic approach revealed cyclophosphamide-induced systematic alterations in a rat model. RSC Adv 6(112):111020–111030.  https://doi.org/10.1039/c6ra18600a CrossRefGoogle Scholar
  28. 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
  29. 29.
    Mansour DF, Salama AAA, Hegazy RR, Omara EA, Nada SA (2017) Whey protein isolate protects against cyclophosphamide-induced acute liver and kidney damage in rats. JAPS 7(06):111–120.  https://doi.org/10.7324/JAPS.2017.70615 Google Scholar
  30. 30.
    Singh D, Whooley MA, Ix JH, Ali S, Shlipak M (2007) Association of cystatin C and estimated GFR with inflammatory biomarkers: the heart and soul study. Nephrol Dial Transplant 22(4):1087–1092.  https://doi.org/10.1093/ndt/gfl744 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Nasseri-Moghaddam S, Ganji MR, Kochari MR, Tofangchiha S (2013) Serum cystatin-C ıs not superior to serum creatinine in predicting glomerular filtration rate in cirrhotic patients. Middle East J Dig Dis 5(4):209–216PubMedPubMedCentralGoogle Scholar
  32. 32.
    Murty MSN, Sharma UK, Pandey VB, Kankare SB (2013) Serum cystatin C as a marker of renal function in detection of early acute kidney injury. Indian J Nephrol 23(3):180–183.  https://doi.org/10.4103/0971-4065.111840 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Stabuc B, Vrhovec L, Stabuc-Silih M, Cizej TE (2000) Improved prediction of decreased creatinine clearance by serum cystatin C: use in cancer patients before and during chemotherapy. Clin Chem 46(2):193–197PubMedGoogle Scholar
  34. 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. 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. 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
  37. 37.
    Song J, Liu L, Li L, Liu J, Song E, Song Y (2014) Protective effects of lipoic acid and mesna on cyclophosphamide-induced haemorrhagic cystitis in mice. Cell Biochem Funct 32(2):125–132.  https://doi.org/10.1002/cbf.2978 CrossRefPubMedGoogle Scholar
  38. 38.
    Murali VP, Kuttan G (2016) Curculigo orchioides gaertn effectively ameliorates the uro- and nephrotoxicities induced by cyclophosphamide administration in experimental animals. Integr Cancer Ther 15(2):205–215.  https://doi.org/10.1177/1534735415607319 CrossRefPubMedGoogle Scholar
  39. 39.
    Liu Q, Lin X, Li H, Yuan J, Peng Y, Dong L, Dai S (2016) Paeoniflorin ameliorates renal function in cyclophosphamide-induced mice via AMPK suppressed inflammation and apoptosis. Biomed Pharmacother 84:1899–1905.  https://doi.org/10.1016/j.biopha.2016.10.097 CrossRefPubMedGoogle Scholar
  40. 40.
    Kocahan S, Dogan Z, Erdemli E, Taskin E (2017) Protective effect of quercetin against oxidative stress-induced toxicity associated with doxorubicin and cyclophosphamide in rat kidney and liver tissue. Iran J Kidney Dis 11(2):124–131PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Faculty of Arts and Science Department of BiologyEskisehir Osmangazi UniversityEskisehirTurkey
  2. 2.Faculty of Medicine Department of Histology and EmbryologyEskisehir Osmangazi UniversityEskisehirTurkey
  3. 3.Faculty of Medicine Department of BiochemistryEskisehir Osmangazi UniversityEskisehirTurkey
  4. 4.Faculty of Medicine Department of PhysiologyEskisehir Osmangazi UniversityEskisehirTurkey

Personalised recommendations

Cite article

Buy options