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Effects of Acute In vivo Cisplatin and Selenium Treatment on Hematological and Oxidative Stress Parameters in Red Blood Cells of Rats

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Abstract

Although cisplatin (cisPt) is one of the most often used cytotoxic drugs in the treatment of cancer, its clinical application is associated with nephrotoxicity and a cumulative anemia. In this study, we evaluated posible protective effects of selenium (Se) on hematological and oxidative stress parameters in rats, acutely treated with cisPt. Four groups of Wistar albino rats included control rats, cisPt-treated (7.5 mg/kg of body weight of cisPt, i.p.), Se-treated (6 mg/kg of body weight of Na2SeO4, i.p.), and Se and cisPt co-treated rats. The rats were killed 72 h after treatment; hematological and oxidative stress parameters were followed in red blood cells. The results showed depletion in platelet number induced by high acute doses of cisPt and strong utilization of reduced glutathione, resulting in elevation of GSSG/2 GSH ratio. Se treatment was followed by stimulated erythropoiesis, increased lipid peroxidation, and GSH depletion. Se and cisPt co-treatment were followed by stimulated erythropoiesis and significant recovery of reduced glutathione status when compared with cisPt-treated rats. In conclusion, acute doses of Se and cisPt primarily act as pro-oxidants. CisPt influenced antioxidative properties of exogenous Se and their synergistic effects may partially participate in protection against cisPt-induced toxicity.

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References

  1. Taguchi T, Nazneen A, Abid MR et al (2005) Cisplatin-associated nephrotoxicity and pathological events. Contrib Nephrol 148:107–121

    Article  PubMed  CAS  Google Scholar 

  2. Perez RP (1998) Cellular and molecular determinants of cisplatin resistance. Eur J Cancer 34:1535–1542

    Article  PubMed  CAS  Google Scholar 

  3. Friesen C, Fulda S, Debatin KM (1999) Cytotoxic drugs and the CD95 pathway. Leukemia 13:1854–1858

    Article  PubMed  CAS  Google Scholar 

  4. Ueda N, Kaushal GP, Shah SV (2000) Apoptotic mechanisms in acute renal failue. Am J Med 108:403–415

    Article  PubMed  CAS  Google Scholar 

  5. Santos NAG, Catao Bezerra CS, Martins NM et al (2008) Hydroxyl radical scavenger ameliorates cisplatin-induced nephrotoxicity by preventing oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria. Cancer Chemother Pharmacol 61:145–155

    Article  PubMed  CAS  Google Scholar 

  6. Berners-Price SJ, Kuchel PW (1990) Reaction of cis- and trans-[PtCl2(NH3)2] with reduced glutatione studied by 1H, 13C, 19Pt, and 15N-{1H}DEPT NMR. J Inorg Biochem 38:305–326

    Article  CAS  Google Scholar 

  7. Durak I, Ozbek H, Karaayvaz M et al (2002) Cisplatin induces acute renal failure by impairing antioxidant system in guinea pigs: effects of antioxidant supplementation on the cisplatin nephrotoxicity. Drug Chem Toxicol 25:1–8

    Article  PubMed  CAS  Google Scholar 

  8. Rayman MP (2000) The importance of selenium to human health. Lancet 356:233–241

    Article  PubMed  CAS  Google Scholar 

  9. Schrauzer GN (2009) Selenium and selenium-antagonistic elements in nutritional cancer prevention. Crit Rev Biotechnol 29:10–17

    Article  PubMed  CAS  Google Scholar 

  10. Suzuki KT, Ogra Y (2002) Metabolic pathway for selenium in the body: speciation by HPLC-ICP MS with enriched Se. Food Addit Contam 19:974–983

    Article  PubMed  CAS  Google Scholar 

  11. Imai T, Mihara H, Kurihara T et al (2009) Selenocysteine is selectively taken up by red blood cells. Biosci Biotechnol Biochem 73:2746–2748

    Article  PubMed  CAS  Google Scholar 

  12. Clark LC, Combs GF, Turnbull BW et al (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA 276:1957–1963

    Article  PubMed  CAS  Google Scholar 

  13. Combs GF Jr, Gray WP (1998) Chemopreventive agents: selenium. Pharmacol Ther 79:179–192

    Article  PubMed  CAS  Google Scholar 

  14. Gudkov AV (2002) Converting p53 from a killer into a healer. Nat Med 8:1196–1198

    Article  PubMed  CAS  Google Scholar 

  15. Seo Y, Kelley M, Smith M (2002) Selenomethionine regulation of p53 by a Ref1-dependent redox mechanism. Proc Natl Acad Sci 99:14548–14553

    Article  PubMed  CAS  Google Scholar 

  16. Dong Y, Ganther HE, Stewart C, Ip C (2002) Identification of molecular targets associated with selenium-induced growth inhibition in human breast cells using cDNA microarrays. Cancer Res 62:708–714

    PubMed  CAS  Google Scholar 

  17. Dong Y, Zhang H, Hawthorn L et al (2003) Delineation of the molecular basis for selenium-induced growth arrest in human prostate cancer cells by oligonucleotide array. Cancer Res 63:52–59

    PubMed  CAS  Google Scholar 

  18. Ip C, Dong Y (2001) Methylselenocysteine modulates proliferation and apoptosis biomarkers in premalignant lesions of the rat mammary gland. Anticancer Res 21:863–867

    PubMed  CAS  Google Scholar 

  19. Lu J, Jiang C, Kaeck M, Ganther H et al (1995) Dissociation of the genotoxic and growth inhibitory effects of selenium. Biochem Pharmacol 50:213–219

    Article  PubMed  CAS  Google Scholar 

  20. Zachara BA, Trafikowska U, Labedzka H et al (1990) Effect of selenium supplementation on glutathione peroxidase synthesis and element accumulation in sheep erythrocytes. Biomed Biochim Acta 49:186–191

    Google Scholar 

  21. Ognjanović BI, Marković SD, Pavlović SZ et al (2008) Effect of chronic cadmium exposure on antioxidant defense system in some tissues of rats: protective effect of selenium. Physiol Res 57:403–411

    PubMed  Google Scholar 

  22. Ayhanci A, Günes S, Sahinturk V et al (2009) Seleno l-methionine acts on cyclophosphamide-induced kidney toxicity. Biol Trace Elem Res. doi:10.1007/s12011-009-8535-2

    Google Scholar 

  23. Hu YJ, Chen Y, Zhang YQ et al (1997) The protective role of selenium on the toxicity of cisplatin-contained chemotherapy regimen in cancer patients. Biol Trace Elem Res 56:331–341

    Article  PubMed  CAS  Google Scholar 

  24. Schrauzer GN (2008) Effects of selenium and low levels of lead on mammary tumor development and growth in MMTV-infected female mice. Biol Trace Elem Res 125:268–275

    Article  PubMed  CAS  Google Scholar 

  25. Sugawara N, Sugawara C (1987) Effect of oral selenium on cadmium absorption from the gastrointestinal tract. Trace Subst Environ Health 21:440–449

    CAS  Google Scholar 

  26. Gregus Z, Gyurasics A, Csanaky I (2000) Effects of arsenic-, platinum-, and gold-containing drugs on the disposition of exogenous selenium in rats. Toxicol Sci 57:22–31

    Article  PubMed  CAS  Google Scholar 

  27. Drabkin D, Austin H (1935) Spectrophotometric studies preparations from washed blood cells. J Biol Chem 112:51–55

    CAS  Google Scholar 

  28. Auclair C, Voisin E (1985) Nitroblue tetrazolium reduction. In: Greenwald RA (ed) Handbook of methods for oxygen radical research. CRC Press, Inc, Boka Raton

    Google Scholar 

  29. Pick E, Keisari Y (1980) A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture. J Immunol Meth 38:161–170

    Article  CAS  Google Scholar 

  30. Green LC, Wagner DA, Glogowski J et al (1982) Analysis of nitrate, nitrite and [15N] nitrate in biological fluids. Anal Biochem 126:131–138

    Article  PubMed  CAS  Google Scholar 

  31. Riordan JF, Vallee BL (1972) Nitration with tetranitromethane. In: Hirs CHW, Timasheff SN (eds) Methods in enzymology. Academic, New York

    Google Scholar 

  32. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  PubMed  CAS  Google Scholar 

  33. Beutler E (1975) Reduced glutathione (GSH). In: Beutler E (ed) Red cell metabolism. A mannual of biochemical methods. Grune and Straton, New York

    Google Scholar 

  34. Hissin PJ, Hilf R (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 74:214–226

    Article  PubMed  CAS  Google Scholar 

  35. Tsuchihashi M (1923) Zur Kernntnis der Blutkatalase. Biochem Z 140:65–74

    Google Scholar 

  36. Marklund S, Marklund G (1974) Involvement of superoxide anion radical in the autoxidation of pyrogallol and convenient assay for superoxide dismutase. Eur J Biochem 47:469–474

    Article  PubMed  CAS  Google Scholar 

  37. Beutler E (1982) Catalase. In: Beutler E (ed) Red cell metabolism. A mannual of biochemical methods. Grune and Stratton, Inc, New York, pp 105–106

    Google Scholar 

  38. Maral J, Puget K, Michelson AM (1977) Comparative study of superoxide dismutase, catalase and glutathione peroxidase levels in erythrocytes of different animals. BBRC 77:1525–1535

    PubMed  CAS  Google Scholar 

  39. Glatzle D, Vuilleumier JP, Weber F et al (1974) Glutathione reductase test with whole blood, a convinient procedure for the assessment of riboflavin status in humans. Experientia 30:665–667

    Article  PubMed  CAS  Google Scholar 

  40. Habig WH, Pabst MJ, Jakobay WB (1974) Glutathione S-transferase. J Biol Chem 249:7130–7139

    PubMed  CAS  Google Scholar 

  41. Naziroglu M, Karaoğlu A, Aksoy AO (2004) Selenium and high dose vitamin E administration protects cisplatin-induced oxidative damage to renal, liver and lens tissues in rats. Toxicology 195:221–230

    Article  PubMed  CAS  Google Scholar 

  42. Wood PA, Hrusheeky WJM (1995) Cisplatin-associated anemia: an erythropoietin deficiency syndrome. J Clin Invest 95:1650–1659

    Article  PubMed  CAS  Google Scholar 

  43. Olas B, Wachowicz B, Majsterek I et al (2005) Resveratrol may reduce oxidative stress induced by platinum compounds in human plasma, blood platelets and lymphocytes. Anticancer Drugs 16:659–665

    Article  PubMed  CAS  Google Scholar 

  44. Brandao R, Lara FS, Pagliosa LB et al (2005) Hemolytic effects of sodium selenite and mercuric chloride in human blood. Drug Chem Toxicol 28:397–407

    Article  PubMed  CAS  Google Scholar 

  45. Steinbrenner H, Bilgic E, Alili L et al (2006) Selenoprotein P protects endothelial cells from oxidative damage by stimulation of glutathione peroxidase expression and activity. Free Radic Res 40:936–943

    Article  PubMed  CAS  Google Scholar 

  46. Agarwal R, Behari JR (2007) Role of selenium in mercury intoxication in mice. Ind Health 45:388–395

    Article  PubMed  CAS  Google Scholar 

  47. Zhang J, Wang H, Peng D et al (2008) Further insight into the impact of sodium selenite on selenoenzymes: high-dose selenite enhances hepatic thioredoxin reductase 1 activity as a consequence of liver injury. Toxicol Lett 176:223–229

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Ministry for Science and Environmental Protection of the Republic of Serbia, Grant No 143035B, and by the CPCTAS project, 7th Framework Program (Regions of knowledge Work Program, Coordination and Support Actions funding scheme), Grant No 206809.

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Authors and Affiliations

  1. Faculty of Science, Department for Biology and Ecology, University of Kragujevac, Radoja Domanovića 12, 34000, Kragujevac, P.O. Box 60, Serbia

    Snežana D. Marković, Dragana S. Djačić, Danijela M. Cvetković, Ana D. Obradović, Jovana B. Žižić, Branka I. Ognjanović & Andraš Š. Štajn

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  1. Snežana D. Marković
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  2. Dragana S. Djačić
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  3. Danijela M. Cvetković
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  4. Ana D. Obradović
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  6. Branka I. Ognjanović
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Correspondence to Snežana D. Marković.

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Marković, S.D., Djačić, D.S., Cvetković, D.M. et al. Effects of Acute In vivo Cisplatin and Selenium Treatment on Hematological and Oxidative Stress Parameters in Red Blood Cells of Rats. Biol Trace Elem Res 142, 660–670 (2011). https://doi.org/10.1007/s12011-010-8788-9

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