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Role of vitamin E-acetate on cisplatin induced genotoxicity: An in vivo analysis

  • Research Article
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Central European Journal of Biology

Abstract

Vitamin E has generated immense interest because of its potential of being an antioxidant, a neuroprotector, and a protector against atherosclerosis, carcinogenesis and cardiovascular disease. However, the prooxidant chemistry of vitamin E cannot be ignored since it is related to the generation of peroxyl radicals. In the present study, 125, 250 and 500 mg/kg of vitamin E-acetate (VE) administered intraperitoneally (i.p.) to Balb/C mice significantly induced 6%, 8% and 11.33% (control value=2.33%) of chromosome aberrations (CA) and 0.88%, 1.39% and 1.81% (control value=0.61%) of micronucleus (MN), following 24 hour of treatment in the bone marrow cells. In the germ cells, VE did not induce any sperm head abnormality (SHA) after 35 days of exposure. Most importantly, it has been observed that pre-treatment with VE significantly reduces CA, MN, and SHA induction by chemotherapeutic drug cisplatin (CIS). Our findings suggest that lone treatment with VE induce genotoxicity in somatic cells after 24 and 48 hours of exposure but not in germ cells after 35 days of exposure, whereas pre-treatment with VE reduces CIS induced genotoxicity as well as cytotoxicity. There exists a thin line of difference on the behavioral transition of VE when acting alone and when acting with a drug.

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References

  1. Traber M.G., Atkinson J., Vitamin E Antioxidant and Nothing More, Free Radic. Biol. Med., 2007, 43, 4–15

    Article  PubMed  CAS  Google Scholar 

  2. Khanna S., Roy S., Slivka A., Craft T.K.S., Cameron S.C., Rink M., et al., Neuroprotective Properties of The Natural Vitamin E-acetate α-Tocotrienol, Stroke., 2005, 36, 2258–2264

    Article  PubMed  Google Scholar 

  3. Khanna S., Roy S., Parinandi N.L., Maurer M., Sen C.K., Characterization of the potent neuroprotective properties of the natural Vitamin E α-tocotrienol, Neurochem., 2006, 98, 1474–1486

    Article  CAS  Google Scholar 

  4. Coulter I.D., Hardy M.L., Morton S.C., Hilton L.G., Wenli T., Di Valentine J.D., et al., Antioxidants Vitamin C and Vitamin E for the Prevention and Treatment of Cancer, J. Gen. Intern. Med., 2006, 21, 735–744

    Article  PubMed  Google Scholar 

  5. Dutta A., Dutta S.K., Vitamin E and its Role in the Prevention of Atherosclerosis and Carcinogenesis: A Review, J. Am. Col. Nutr., 2003, 22, 258–268

    CAS  Google Scholar 

  6. Shekelle P.G., Morton S.C., Jungvig L.K., Udani J., Spar M., Tu W., et al., Effect of Supplemental Vitamin E for the Prevention and Treatment of Cardiovascular Disease, J. Gen. Intern Med., 2004, 19, 380–389

    Article  PubMed  Google Scholar 

  7. Reiter E., Jiang Q., Christena S., Anti-inflammatory properties of α- and γ-tocopherol, Mol. Aspects Med., 2007, 28, 668–691

    Article  PubMed  CAS  Google Scholar 

  8. Kumar B.J., Mitra N., Cole W.C., Bedford J.S., Prasad K.N., D-Alpha-Tocopheryl Succinate (Vitamin E-acetate) Enhances Radiation-Induced Chromosomal Damage Levels in Human Cancer Cells, but Reduces it in Normal Cells, FACN J. Am. Col. Nutr., 2002, 21, 339–343

    CAS  Google Scholar 

  9. Hemila H., Kaprio J., Vitamin E-acetate supplementation and pneumonia risk in males who initiated smoking at an early age: effect modification by body weight and dietary vitamin C, Nutr J., 2008, 7:33

    Article  PubMed  Google Scholar 

  10. Myers C.E., McGuire W.P., Liss R.H., Ifrim I., Grotzinger K., Young R.C., Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response, Science., 1977, 197, 165–167

    Article  PubMed  CAS  Google Scholar 

  11. Ripoll E.A.P., Rama B.N., Webber M.M., Vitamin E enhances the chemotherapeutic effects of adriamycin on human prostatic carcinoma cells in vitro, J. Urol., 1986, 136, 529–531

    PubMed  CAS  Google Scholar 

  12. Appenroth D., Frob S., Kersten L., Splinter F.K., Winnefeld K., Protective effects of Vitamin E and C on Cisplatin nephrotoxicity in developing rats, Arch. Toxicol, 1997, 71, 677–683

    Article  PubMed  CAS  Google Scholar 

  13. Pace A., Savarese A., Picardo M., Maresca V., Pacetti U., Del Monte G., et al., Neuroprotective Effect of Vitamin E Supplementation in Patients Treated With Cisplatin Chemotherapy, J. Clin. Oncol., 2003, 21, 927–931

    Article  PubMed  CAS  Google Scholar 

  14. Preston R.J., Dean B.J., Galloway S., Holden H., McFe A.F., Shelby M., Mammalian in vivo cytogenetic assays: analysis of chromosome aberrations in bone marrow cells, Mutat. Res., 1987, 189, 157–165

    Article  PubMed  CAS  Google Scholar 

  15. Krishna G., Theiss J.C., Concurrent analysis of cytogenetic damage in vivo: a multiple endpointmultiple tissue approach, Environ. Mol. Mutagen., 1995, 25, 314–320

    Article  PubMed  CAS  Google Scholar 

  16. Schmid W., The micronucleus test for cytogenetic analysis. In: Hollaender A editor. Chemical mutagens: Principles and methods for their detection, New York: Plenum Press., 1976, 4, 31–53

    Google Scholar 

  17. Wyrobek A.J., Bruce W.R., Induction of sperm shape abnormalities in mice and humans, In Chemical Mutagens, Principles and Methods for their Detection, Plenum Press, New York, 1978

    Google Scholar 

  18. Curran S.P., Wu X., Riedel C.G., Ruvkun, G., A soma-to-germline transformation in long-lived Caenorhabditis elegans mutants, Nature, 2009, 459, 1079–1084

    Article  PubMed  CAS  Google Scholar 

  19. Jones D.L., Walk the (Germ) line, Cell Metabolism, 2009, 10, 78–79

    Article  PubMed  CAS  Google Scholar 

  20. Kaminski R., Darbinyan, A., Merabova, N., Deshmane, S.L., White, M.K., Khalili, K., Protective role of Purα to Cisplatin, Cancer Biol Ther., 2008, 7, 1926–1935

    Article  PubMed  CAS  Google Scholar 

  21. Li A.P., Heflich R.H., Genetical Toxicology, CRC Press, 1991

  22. Satoh M., Kashihara N., Fujimoto S., Horike H., Tokura T., Namikoshi T., et al., A novel free radical scavenger, edarabone, protects against cisplatininduced acute renal damage in vitro and in vivo, J Pharmacol Exp Ther, 2003, 305, 1183–1190

    Article  PubMed  CAS  Google Scholar 

  23. Brozovic A., Ambriović-Ristov A., Osmak M., The relationship between Cisplatin induced reactive oxygen species, glutathione and BCL-2 and resistance to cisplatin, Crit. Rev toxicology., 2010, 40, 347–59

    Article  CAS  Google Scholar 

  24. Florea A.M., Büsselberg D., Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects, Cancers, 2011, 3, 1351–1371

    CAS  Google Scholar 

  25. Masuda H., Tanaka T., Takahama U., Cisplatin generates superoxide anion by interaction with DNA in a cell-free system, Biochem. Biophys. Res. Commun., 1994, 2031, 1175–1180

    Article  Google Scholar 

  26. Jackson R.L., Oates J.A., Linton M.F., Fazio S., Meador B.P.M., Gross D., et al., The Relationship between Dose of Vitamin E-acetate and Suppression of Oxidative Stress in Humans, Free Radic. Biol.Med., 2007, 43, 1388–1393

    Article  Google Scholar 

  27. Sorenson C.M., Eastman A., Mechanism of cis-diammine-dichloroplatinum_II.-induced cytotoxicity: Role of G2 arrest and DNA doublestrand breaks, Cancer Res., 1988, 48, 6703–6707

    PubMed  CAS  Google Scholar 

  28. Ingold K., Webb A., Witter D, Burton G., Metcalfe T., Muller D., Vitamin E-acetate remains the major lipid soluble chain breaking antioxidant in human plasma even in individuals suffering severe Vitamin E-acetate deficiency, Arch. Biochem. Biophys., 1987, 259, 224–225

    Article  PubMed  CAS  Google Scholar 

  29. Omara F.O., Blakeley B.R., Vitamin E Is Protective against Iron Toxicity and Iron-Induced Hepatic Vitamin E-acetate Depletion in Mice, J. Nutr., 1993, 123, 1649–1655

    PubMed  CAS  Google Scholar 

  30. Kan E., Undeger U., Bali M., Basaran N., Assessment of DNA strand breakage by the alkaline COMET assay in dialysis patients and the role of Vitamin E-acetate supplementation, Mutat. Res., 2002, 520, 151–159

    PubMed  CAS  Google Scholar 

  31. Rao V.M., Parekh S.S., Chawla L.S., Vitamin E supplementation ameliorates chromium — and/or nickel induced oxidative stress in vivo, J. Health Sci., 2006, 52, 142–147

    Article  CAS  Google Scholar 

  32. Fantappie O., Lodovici M., Fabrizio P., Marchetti S., Fabbroni V., Solazzo M., et al., Vitamin E-acetate Protects DNA from Oxidative Damage in Human Hepatocellular Carcinoma Cell Lines, Free Radical Res., 2004, 38, 751–759

    Article  CAS  Google Scholar 

  33. Velanganni, A.A., Balasundaram, C., Protective effect of vitamin A, ascorbic acid and a — tocopherol on 2, 4-dimethyaminoazobenzene-induced hepatoma in rats, Curr Sci., 2003, 85, 201–203

    CAS  Google Scholar 

  34. Jenkinson A.M., Collin A.R., Duthie S.J., Wahle K.W.J., Duthie G.G., The effect of increased intakes of polyunsaturated fatty acids sand Vitamin E-acetate on DNA damage in human lymphocytes, FASEB J., 1999, 13, 2138–2142

    PubMed  CAS  Google Scholar 

  35. Nouri M., Ghasemzadeh A., Farzadi L., Shahnazi V., Novin M.G., Vitamins C, E and lipid peroxidation levels in sperm and seminal plasma of asthenoteratozoospermic and normozoospermic men, Iranian J. Rep. Med., 2008, 6, 1–5

    CAS  Google Scholar 

  36. Brigelius-Flohe R., Induction of drug metabolizing enzymes by Vitamin E, J Plant Physiol, 2005, 162, 797–802

    Article  PubMed  CAS  Google Scholar 

  37. Bowry V.W., Stocker R., Tocopherol-mediated peroxidation. The pro-oxidant effect of Vitamin E on the radical-initiated oxidation of human lowdensity lipoprotein, J Am Chem. Soc., 1993, 115, 6029–6044

    Article  CAS  Google Scholar 

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Correspondence to Mehnaz Mazumdar.

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Mazumdar, M., Giri, S. & Roy, S. Role of vitamin E-acetate on cisplatin induced genotoxicity: An in vivo analysis. cent.eur.j.biol. 7, 334–342 (2012). https://doi.org/10.2478/s11535-012-0001-z

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  • DOI: https://doi.org/10.2478/s11535-012-0001-z

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