Display options
Cite
Millán M, DeGregorio-Rocasolano N, Pérez de la Ossa N, et al. Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial. Antioxidants (Basel). 2021;10(8)doi: 10.3390/antiox10081270.
Millán, M., DeGregorio-Rocasolano, N., Pérez de la Ossa, N., Reverté, S., Costa, J., Giner, P., Silva, Y., Sobrino, T., Rodríguez-Yáñez, M., Nombela, F., Campos, F., Serena, J., Vivancos, J., Martí-Sistac, O., Cortés, J., Dávalos, A., & Gasull, T. (2021). Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial. Antioxidants (Basel, Switzerland), 10(8), . https://doi.org/10.3390/antiox10081270
Millán, Mònica, et al. "Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial." Antioxidants (Basel, Switzerland) vol. 10,8 (2021). doi: https://doi.org/10.3390/antiox10081270
Millán M, DeGregorio-Rocasolano N, Pérez de la Ossa N, Reverté S, Costa J, Giner P, Silva Y, Sobrino T, Rodríguez-Yáñez M, Nombela F, Campos F, Serena J, Vivancos J, Martí-Sistac O, Cortés J, Dávalos A, Gasull T. Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial. Antioxidants (Basel). 2021 Aug 10;10(8). doi: 10.3390/antiox10081270. PMID: 34439518; PMCID: PMC8389327.
Copy Download .nbib Format: NLM
Share it on

Antioxidants (Basel). 2021 Aug 10;10(8). doi: 10.3390/antiox10081270.

Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial.

Antioxidants (Basel, Switzerland)

Mònica Millán, Núria DeGregorio-Rocasolano, Natàlia Pérez de la Ossa, Sílvia Reverté, Joan Costa, Pilar Giner, Yolanda Silva, Tomás Sobrino, Manuel Rodríguez-Yáñez, Florentino Nombela, Francisco Campos, Joaquín Serena, José Vivancos, Octavi Martí-Sistac, Jordi Cortés, Antoni Dávalos, Teresa Gasull

Affiliations

  1. Department of Neurosciences, Hospital Germans Trias i Pujol, 08916 Badalona, Barcelona, Spain.
  2. Cellular and Molecular Neurobiology Research Group, Department of Neurosciences, Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Barcelona, Spain.
  3. Department of Clinical Pharmacology, Hospital Germans Trias i Pujol, 08916 Badalona, Barcelona, Spain.
  4. Department of Pharmacy, Hospital Germans Trias i Pujol, 08916 Badalona, Barcelona, Spain.
  5. Department of Neurology, Hospital Dr. Josep Trueta, 17007 Girona, Spain.
  6. Clinical Neurosciences Research Laboratory, Health Research Institute of Santiago de Compostela, Hospital Clínico Universitario, Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain.
  7. Department of Neurology, Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain.
  8. Department of Neurology, Hospital La Princesa, 28006 Madrid, Spain.
  9. Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
  10. Department of Statistics and Operations Research, Universitat Politècnica de Catalunya (UPC), 08028 Barcelona, Spain.

PMID: 34439518 PMCID: PMC8389327 DOI: 10.3390/antiox10081270

Abstract

A role of iron as a target to prevent stroke-induced neurodegeneration has been recently revisited due to new evidence showing that ferroptosis inhibitors are protective in experimental ischemic stroke and might be therapeutic in other neurodegenerative brain pathologies. Ferroptosis is a new form of programmed cell death attributed to an overwhelming lipidic peroxidation due to excessive free iron and reactive oxygen species (ROS). This study aims to evaluate the safety and tolerability and to explore the therapeutic efficacy of the iron chelator and antioxidant deferoxamine mesylate (DFO) in ischemic stroke patients. Administration of placebo or a single DFO bolus followed by a 72 h continuous infusion of three escalating doses was initiated during the tPA infusion, and the impact on blood transferrin iron was determined. Primary endpoint was safety and tolerability, and secondary endpoint was good clinical outcome (clinicalTrials.gov NCT00777140). DFO was found safe as adverse effects were not different between placebo and DFO arms. DFO (40-60 mg/Kg/day) reduced the iron saturation of blood transferrin. A trend to efficacy was observed in patients with moderate-severe ischemic stroke (NIHSS > 7) treated with DFO 40-60 mg/Kg/day. A good outcome was observed at day 90 in 31% of placebo vs. 50-58% of the 40-60 mg/Kg/day DFO-treated patients.

Keywords: antioxidant; deferoxamine; ferroptosis; iron; neuroprotection; outcome

References

  1. World Neurosurg. 2019 Aug;128:e895-e904 - PubMed
  2. J Biol Inorg Chem. 2008 Feb;13(2):229-40 - PubMed
  3. Talanta. 1997 Dec 12;45(1):25-33 - PubMed
  4. Stroke. 2011 Nov;42(11):3067-74 - PubMed
  5. Blood. 1996 Jul 15;88(2):705-13 - PubMed
  6. PLoS One. 2015 Apr 13;10(4):e0122371 - PubMed
  7. Eur J Med Chem. 2021 Jan 1;209:112842 - PubMed
  8. Neurocrit Care. 2013 Oct;19(2):257-66 - PubMed
  9. J Pharmacol Exp Ther. 2009 Sep;330(3):679-86 - PubMed
  10. Lancet Neurol. 2019 May;18(5):428-438 - PubMed
  11. Eur J Neurosci. 2006 Apr;23(7):1757-65 - PubMed
  12. Brain Res Bull. 2019 Nov;153:122-132 - PubMed
  13. Stroke. 2003 Dec;34(12):2964-9 - PubMed
  14. Drug Metab Dispos. 1993 Jul-Aug;21(4):640-4 - PubMed
  15. Stroke. 2001 Feb;32(2):438-41 - PubMed
  16. Int J Pharm. 2018 Mar 1;538(1-2):79-86 - PubMed
  17. Brain Res Bull. 2021 Jul;172:212-219 - PubMed
  18. Life Sci. 2020 Nov 1;260:118305 - PubMed
  19. J Integr Med. 2020 Jul;18(4):344-350 - PubMed
  20. Lancet. 2007 Jan 27;369(9558):275-82 - PubMed
  21. Stroke. 2010 Apr;41(4):810-3 - PubMed
  22. Technol Cancer Res Treat. 2018 Jan 1;17:1533033818764470 - PubMed
  23. Stroke. 2018 Sep;49(9):2163-2172 - PubMed
  24. J Trace Elem Med Biol. 2015;31:260-6 - PubMed
  25. N Engl J Med. 2005 Apr 28;352(17):1769-78 - PubMed
  26. Redox Biol. 2018 May;15:143-158 - PubMed
  27. PLoS One. 2015 May 22;10(5):e0127256 - PubMed
  28. Ann Neurol. 2018 Dec;84(6):854-872 - PubMed
  29. Front Neurosci. 2019 Feb 19;13:85 - PubMed
  30. Am J Physiol Regul Integr Comp Physiol. 2004 Feb;286(2):R283-8 - PubMed
  31. Transl Stroke Res. 2021 Aug;12(4):615-630 - PubMed
  32. CNS Drugs. 2021 Jan;35(1):85-104 - PubMed
  33. Mol Psychiatry. 2017 Nov;22(11):1520-1530 - PubMed
  34. Dev Neurosci. 2018;40(5-6):382-395 - PubMed
  35. J Cereb Blood Flow Metab. 2011 Jun;31(6):1412-23 - PubMed
  36. Br J Haematol. 1979 Aug;42(4):547-55 - PubMed
  37. Neurology. 2000 Apr 25;54(8):1568-74 - PubMed
  38. Stroke. 2008 Apr;39(4):1165-70 - PubMed
  39. Stroke. 1994 May;25(5):1039-45 - PubMed
  40. Neurosci Bull. 2008 Apr;24(2):89-95 - PubMed
  41. Brain Res. 2002 Oct 11;952(1):1-6 - PubMed
  42. Indian J Med Res. 2018 Oct;148(4):369-372 - PubMed
  43. Br J Clin Pharmacol. 1987 Aug;24(2):207-12 - PubMed
  44. Stroke. 2007 Jan;38(1):90-5 - PubMed
  45. Acta Biochim Biophys Sin (Shanghai). 2017 Sep 1;49(9):827-834 - PubMed
  46. J Neurosurg. 2004 Apr;100(4):672-8 - PubMed
  47. Brain Res. 2012 May 21;1455:114-23 - PubMed
  48. Clin Neurol Neurosurg. 2021 Mar;202:106494 - PubMed
  49. Brain Res. 2009 Sep 29;1291:113-21 - PubMed
  50. Am J Clin Nutr. 2021 Aug 2;114(2):780-793 - PubMed
  51. Front Pharmacol. 2021 Jun 04;12:657033 - PubMed
  52. Exp Eye Res. 2018 Jun;171:30-36 - PubMed
  53. Ann N Y Acad Sci. 2005;1054:155-68 - PubMed

Publication Types

Grant support