Display options
Cite
Attia SM, Ahmad SF, Ansaria MA, et al. Utility of Dexrazoxane for the Attenuation of Epirubicin-Induced Genetic Alterations in Mouse Germ Cells. PLoS One. 2016;11(9):e0163703doi: 10.1371/journal.pone.0163703.
Attia, S. M., Ahmad, S. F., Ansaria, M. A., Nadeem, A., Al-Shabanah, O. A., Al-Harbi, M. M., & Bakheet, S. A. (2016). Utility of Dexrazoxane for the Attenuation of Epirubicin-Induced Genetic Alterations in Mouse Germ Cells. PloS one, 11(9), e0163703. https://doi.org/10.1371/journal.pone.0163703
Attia, Sabry M, et al. "Utility of Dexrazoxane for the Attenuation of Epirubicin-Induced Genetic Alterations in Mouse Germ Cells." PloS one vol. 11,9 (2016): e0163703. doi: https://doi.org/10.1371/journal.pone.0163703
Attia SM, Ahmad SF, Ansaria MA, Nadeem A, Al-Shabanah OA, Al-Harbi MM, Bakheet SA. Utility of Dexrazoxane for the Attenuation of Epirubicin-Induced Genetic Alterations in Mouse Germ Cells. PLoS One. 2016 Sep 30;11(9):e0163703. doi: 10.1371/journal.pone.0163703. eCollection 2016. PMID: 27690233; PMCID: PMC5045162.
Copy Download .nbib Format: NLM
Share it on

PLoS One. 2016 Sep 30;11(9):e0163703. doi: 10.1371/journal.pone.0163703. eCollection 2016.

Utility of Dexrazoxane for the Attenuation of Epirubicin-Induced Genetic Alterations in Mouse Germ Cells.

PloS one

Sabry M Attia, Sheikh F Ahmad, Mushtaq A Ansaria, Ahmed Nadeem, Othman A Al-Shabanah, Mohammed M Al-Harbi, Saleh A Bakheet

Affiliations

  1. Pharmacology and Toxicology Department, Faculty of Pharmacy, King Saud University, 11451, Riyadh, Saudi Arabia.
  2. Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.

PMID: 27690233 PMCID: PMC5045162 DOI: 10.1371/journal.pone.0163703

Abstract

Dexrazoxane has been approved to treat anthracycline-induced cardiomyopathy and extravasation. However, the effect of dexrazoxane on epirubicin-induced genetic alterations in germ cells has not yet been reported. Thus, the aim of this study was to determine whether dexrazoxane modulates epirubicin-induced genetic damage in the germ cells of male mice. Our results show that dexrazoxane was not genotoxic at the tested doses. Furthermore, it protected mouse germ cells against epirubicin-induced genetic alterations as detected by the reduction in disomic and diploid sperm, spermatogonial chromosomal aberrations, and abnormal sperm heads. The attenuating effect of dexrazoxane was greater at higher dose, indicating a dose-dependent effect. Moreover, sperm motility and count were ameliorated by dexrazoxane pretreatment. Epirubicin induced marked biochemical changes characteristic of oxidative DNA damage including elevated 8-hydroxy-2'-deoxyguanosine levels and reduction in reduced glutathione. Pretreatment of mice with dexrazoxane before epirubicin challenge restored these altered endpoints. We conclude that dexrazoxane may efficiently mitigate the epirubicin insult in male germ cells, and prevent the enhanced risk of abnormal reproductive outcomes and associated health risks. Thus, pretreating patients with dexrazoxane prior to epirubicin may efficiently preserve not only sperm quality but also prevent the transmission of genetic damage to future generations.

Conflict of interest statement

The authors have declared that no competing interests exist.

References

  1. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4425-9 - PubMed
  2. N Engl J Med. 2004 Jul 8;351(2):145-53 - PubMed
  3. Asian J Androl. 2006 Mar;8(2):143-57 - PubMed
  4. Hum Reprod. 2007 Jul;22(7):1893-8 - PubMed
  5. Cytogenet Genome Res. 2004;107(1-2):83-94 - PubMed
  6. J Clin Biochem Nutr. 2010 Nov;47(3):238-45 - PubMed
  7. Mutat Res. 2009 Feb 19;673(1):29-36 - PubMed
  8. Biomed Pharmacother. 2010 Apr;64(4):259-63 - PubMed
  9. Drugs. 1997;54 Suppl 4:1-7 - PubMed
  10. Clin Cancer Res. 2005 May 15;11(10):3915-24 - PubMed
  11. Cardiovasc Toxicol. 2002;2(2):111-8 - PubMed
  12. J Inorg Biochem. 2000 Feb;78(3):209-16 - PubMed
  13. Zygote. 1999 May;7(2):131-4 - PubMed
  14. BMC Cancer. 2010 Jun 29;10:337 - PubMed
  15. Biosci Rep. 1987 Aug;7(8):653-8 - PubMed
  16. Oxid Med Cell Longev. 2010 Jul-Aug;3(4):238-53 - PubMed
  17. Eur J Hum Genet. 2001 Dec;9(12):910-6 - PubMed
  18. Mutat Res. 1973 Dec;20(3):403-16 - PubMed
  19. Biochem Pharmacol. 1999 Apr 1;57(7):727-41 - PubMed
  20. Mutat Res. 1986 Mar;160(1):39-46 - PubMed
  21. Mutagenesis. 2011 Jul;26(4):533-43 - PubMed
  22. Mol Cancer Ther. 2009 May;8(5):1075-85 - PubMed
  23. Arch Biochem Biophys. 1959 May;82(1):70-7 - PubMed
  24. J Clin Oncol. 1992 Sep;10(9):1444-51 - PubMed
  25. Environ Mol Mutagen. 1996;28(3):159-66 - PubMed
  26. Teratog Carcinog Mutagen. 2002;22(4):257-69 - PubMed
  27. Mutat Res. 2002 Sep 26;520(1-2):1-13 - PubMed
  28. Mutagenesis. 2001 Jul;16(4):339-43 - PubMed
  29. Mutat Res. 2012 Jan 24;741(1-2):22-31 - PubMed
  30. Drug Resist Updat. 2001 Oct;4(5):303-13 - PubMed
  31. Leuk Res. 2003 Jul;27(7):617-26 - PubMed
  32. Ann Oncol. 2006 Apr;17(4):614-22 - PubMed
  33. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD003917 - PubMed
  34. J Biol Chem. 1951 Nov;193(1):265-75 - PubMed
  35. Nat Rev Genet. 2012 Jan 24;13(3):189-203 - PubMed
  36. Mutagenesis. 2016 Mar;31(2):137-45 - PubMed
  37. Z Naturforsch C. 2010 Mar-Apr;65(3-4):211-7 - PubMed
  38. CA Cancer J Clin. 2005 Jul-Aug;55(4):211-28; quiz 263-4 - PubMed
  39. J Clin Oncol. 2005 Jun 20;23(18):4179-91 - PubMed
  40. PLoS One. 2014 Oct 10;9(10):e109942 - PubMed
  41. Mutat Res. 2000 Jul 10;468(2):109-15 - PubMed
  42. Cancer Chemother Pharmacol. 2009 Sep;64(4):837-45 - PubMed
  43. Free Radic Biol Med. 2000 Feb 15;28(4):529-36 - PubMed

Publication Types