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Martínez-Espinosa R, Argüello-García R, Saavedra E, et al. Albendazole induces oxidative stress and DNA damage in the parasitic protozoan Giardia duodenalis. Front Microbiol. 2015;6:800doi: 10.3389/fmicb.2015.00800.
Martínez-Espinosa, R., Argüello-García, R., Saavedra, E., & Ortega-Pierres, G. (2015). Albendazole induces oxidative stress and DNA damage in the parasitic protozoan Giardia duodenalis. Frontiers in microbiology, 6800. https://doi.org/10.3389/fmicb.2015.00800
Martínez-Espinosa, Rodrigo, et al. "Albendazole induces oxidative stress and DNA damage in the parasitic protozoan Giardia duodenalis." Frontiers in microbiology vol. 6 (2015): 800. doi: https://doi.org/10.3389/fmicb.2015.00800
Martínez-Espinosa R, Argüello-García R, Saavedra E, Ortega-Pierres G. Albendazole induces oxidative stress and DNA damage in the parasitic protozoan Giardia duodenalis. Front Microbiol. 2015 Aug 06;6:800. doi: 10.3389/fmicb.2015.00800. eCollection 2015. PMID: 26300866; PMCID: PMC4526806.
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Front Microbiol. 2015 Aug 06;6:800. doi: 10.3389/fmicb.2015.00800. eCollection 2015.

Albendazole induces oxidative stress and DNA damage in the parasitic protozoan Giardia duodenalis.

Frontiers in microbiology

Rodrigo Martínez-Espinosa, Raúl Argüello-García, Emma Saavedra, Guadalupe Ortega-Pierres

Affiliations

  1. Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional México City, Mexico.
  2. Department of Biochemistry, Instituto Nacional de Cardiología Ignacio Chávez México City, Mexico.

PMID: 26300866 PMCID: PMC4526806 DOI: 10.3389/fmicb.2015.00800

Abstract

The control of Giardia duodenalis infections is carried out mainly by drugs, among these albendazole (ABZ) is commonly used. Although the cytotoxic effect of ABZ usually involves binding to β-tubulin, it has been suggested that oxidative stress may also play a role in its parasiticidal mechanism. In this work the effect of ABZ in Giardia clones that are susceptible or resistant to different concentrations (1.35, 8, and 250 μM) of this drug was analyzed. Reactive oxygen species (ROS) were induced by ABZ in susceptible clones and this was associated with a decrease in growth that was alleviated by cysteine supplementation. Remarkably, ABZ-resistant clones exhibited partial cross-resistance to H2O2, whereas a Giardia H2O2-resistant strain can grow in the presence of ABZ. Lipid oxidation and protein carbonylation in ABZ-treated parasites did not show significant differences as compared to untreated parasites; however, ABZ induced the formation of 8OHdG adducts and DNA degradation, indicating nucleic acid oxidative damage. This was supported by observations of histone H2AX phosphorylation in ABZ-susceptible trophozoites treated with 250 μM ABZ. Flow cytometry analysis showed that ABZ partially arrested cell cycle in drug-susceptible clones at G2/M phase at the expense of cells in G1 phase. Also, ABZ treatment resulted in phosphatidylserine exposure on the parasite surface, an event related to apoptosis. All together these data suggest that ROS induced by ABZ affect Giardia genetic material through oxidative stress mechanisms and subsequent induction of apoptotic-like events.

Keywords: DNA damage; Giardia duodenalis; albendazole; apoptosis; oxidative stress

References

  1. Crit Rev Microbiol. 2002;28(2):123-47 - PubMed
  2. Microb Drug Resist. 1996 Fall;2(3):303-8 - PubMed
  3. Appl Environ Microbiol. 2013 Jul;79(13):3943-51 - PubMed
  4. J Antimicrob Chemother. 2007 Aug;60(2):280-7 - PubMed
  5. J Proteomics. 2011 Oct 19;74(11):2228-42 - PubMed
  6. Nat Rev Microbiol. 2010 Jun;8(6):413-22 - PubMed
  7. Drug Des Devel Ther. 2009 Sep 21;3:103-10 - PubMed
  8. J Mol Graph Model. 2004 Dec;23(3):275-84 - PubMed
  9. Curr Infect Dis Rep. 2014 Feb;16(2):396 - PubMed
  10. J Antimicrob Chemother. 2000 Nov;46(5):819-21 - PubMed
  11. PLoS Negl Trop Dis. 2014 Jan 09;8(1):e2631 - PubMed
  12. Indian Pediatr. 2013 Nov 8;50(11):1064 - PubMed
  13. Infect Genet Evol. 2009 Dec;9(6):1057-64 - PubMed
  14. J Biol Chem. 2010 Apr 9;285(15):11154-61 - PubMed
  15. Antioxid Redox Signal. 2012 Aug 15;17(4):555-82 - PubMed
  16. Infect Genet Evol. 2013 Apr;15:10-7 - PubMed
  17. Mutat Res. 2006 May 11;597(1-2):73-7 - PubMed
  18. Redox Rep. 2004;9(2):89-95 - PubMed
  19. Trans R Soc Trop Med Hyg. 1983;77(4):487-8 - PubMed
  20. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14373-7 - PubMed
  21. J Protozool. 1992 Jul-Aug;39(4):510-5 - PubMed
  22. Gene. 2014 Feb 10;535(2):131-9 - PubMed
  23. Chem Res Toxicol. 1998 Oct;11(10 ):1176-83 - PubMed
  24. Curr Opin Infect Dis. 2011 Oct;24(5):451-6 - PubMed
  25. Exp Parasitol. 2010 Feb;124(2):159-66 - PubMed
  26. J Clin Invest. 2013 Jun;123(6):2346-7 - PubMed
  27. Exp Parasitol. 1999 May;92(1):1-11 - PubMed
  28. Int J Parasitol. 2002 Jun;32(6):655-75 - PubMed
  29. Front Microbiol. 2015 Apr 10;6:286 - PubMed
  30. Xenobiotica. 2010 Sep;40(9):593-601 - PubMed
  31. Vet Parasitol. 2012 May 25;186(3-4):364-75 - PubMed
  32. Antimicrob Agents Chemother. 2009 Feb;53(2):458-64 - PubMed
  33. Exp Parasitol. 2005 May;110(1):62-72 - PubMed
  34. J Vet Pharmacol Ther. 2000 Jun;23(3):113-20 - PubMed
  35. PLoS Negl Trop Dis. 2013 May 30;7(5):e2247 - PubMed
  36. Parasitology. 2012 Jun;139(7):894-903 - PubMed
  37. Toxicology. 2007 Jan 5;229(1-2):123-35 - PubMed
  38. Antimicrob Agents Chemother. 2015 Apr;59(4):2242-55 - PubMed
  39. Can J Microbiol. 2014 Dec;60(12):783-91 - PubMed
  40. Parasit Vectors. 2013 Aug 12;6:236 - PubMed
  41. Exp Parasitol. 2010 Jan;124(1):45-53 - PubMed
  42. Mol Cell Biochem. 2013 Apr;376(1-2):121-35 - PubMed
  43. Infect Disord Drug Targets. 2010 Aug;10(4):295-302 - PubMed
  44. Clin Microbiol Rev. 2001 Jan;14(1):114-28 - PubMed
  45. Mol Microbiol. 2006 Jan;59(1):202-11 - PubMed
  46. Mol Biochem Parasitol. 2013 Jan;187(1):72-6 - PubMed
  47. Mol Biochem Parasitol. 2014 Dec;198(2):75-81 - PubMed
  48. Acta Trop. 2003 May;86(2-3):141-59 - PubMed
  49. Int J Parasitol Drugs Drug Resist. 2012 Dec 1;2:47-57 - PubMed
  50. PLoS Negl Trop Dis. 2010 May 11;4(5):e682 - PubMed
  51. Trans R Soc Trop Med Hyg. 2012 Mar;106(3):167-73 - PubMed
  52. Int J Hyg Environ Health. 2010 Sep;213(5):321-33 - PubMed
  53. PLoS Negl Trop Dis. 2014 Oct 16;8(10 ):e3231 - PubMed
  54. Clin Microbiol Rev. 2001 Jan;14(1):150-64 - PubMed

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