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Comparison of various iron chelators and prochelators as protective agents against cardiomyocyte oxidative injury.

Publication ,  Journal Article
Jansová, H; Macháček, M; Wang, Q; Hašková, P; Jirkovská, A; Potůčková, E; Kielar, F; Franz, KJ; Simůnek, T
Published in: Free radical biology & medicine
September 2014

Oxidative stress is a common denominator of numerous cardiovascular disorders. Free cellular iron catalyzes the formation of highly toxic hydroxyl radicals, and iron chelation may thus be an effective therapeutic approach. However, using classical iron chelators in diseases without iron overload poses risks that necessitate more advanced approaches, such as prochelators that are activated to chelate iron only under disease-specific oxidative stress conditions. In this study, three cell-membrane-permeable iron chelators (clinically used deferasirox and experimental SIH and HAPI) and five boronate-masked prochelator analogs were evaluated for their ability to protect cardiac cells against oxidative injury induced by hydrogen peroxide. Whereas the deferasirox-derived agents TIP and TRA-IMM displayed negligible protection and even considerable toxicity, the aroylhydrazone prochelators BHAPI and BSIH-PD provided significant cytoprotection and displayed lower toxicity after prolonged cellular exposure compared to their parent chelators HAPI and SIH, respectively. Overall, the most favorable properties in terms of protective efficiency and low inherent cytotoxicity were observed with the aroylhydrazone prochelator BSIH. BSIH efficiently protected both H9c2 rat cardiomyoblast-derived cells and isolated primary rat cardiomyocytes against hydrogen peroxide-induced mitochondrial and lysosomal dysregulation and cell death. At the same time, BSIH was nontoxic at concentrations up to its solubility limit (600 μM) and in 72-h incubation. Hence, BSIH merits further investigation for prevention and/or treatment of cardiovascular disorders associated with a known (or presumed) component of oxidative stress.

Duke Scholars

Published In

Free radical biology & medicine

DOI

EISSN

1873-4596

ISSN

0891-5849

Publication Date

September 2014

Volume

74

Start / End Page

210 / 221

Related Subject Headings

  • Triazoles
  • Semicarbazones
  • Rats, Wistar
  • Rats
  • Oxidative Stress
  • Myocytes, Cardiac
  • Mitochondria, Heart
  • Membrane Potential, Mitochondrial
  • Isonicotinic Acids
  • Iron Chelating Agents
 

Citation

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Jansová, H., Macháček, M., Wang, Q., Hašková, P., Jirkovská, A., Potůčková, E., … Simůnek, T. (2014). Comparison of various iron chelators and prochelators as protective agents against cardiomyocyte oxidative injury. Free Radical Biology & Medicine, 74, 210–221. https://doi.org/10.1016/j.freeradbiomed.2014.06.019
Jansová, Hana, Miloslav Macháček, Qin Wang, Pavlína Hašková, Anna Jirkovská, Eliška Potůčková, Filip Kielar, Katherine J. Franz, and Tomáš Simůnek. “Comparison of various iron chelators and prochelators as protective agents against cardiomyocyte oxidative injury.Free Radical Biology & Medicine 74 (September 2014): 210–21. https://doi.org/10.1016/j.freeradbiomed.2014.06.019.
Jansová H, Macháček M, Wang Q, Hašková P, Jirkovská A, Potůčková E, et al. Comparison of various iron chelators and prochelators as protective agents against cardiomyocyte oxidative injury. Free radical biology & medicine. 2014 Sep;74:210–21.
Jansová, Hana, et al. “Comparison of various iron chelators and prochelators as protective agents against cardiomyocyte oxidative injury.Free Radical Biology & Medicine, vol. 74, Sept. 2014, pp. 210–21. Epmc, doi:10.1016/j.freeradbiomed.2014.06.019.
Jansová H, Macháček M, Wang Q, Hašková P, Jirkovská A, Potůčková E, Kielar F, Franz KJ, Simůnek T. Comparison of various iron chelators and prochelators as protective agents against cardiomyocyte oxidative injury. Free radical biology & medicine. 2014 Sep;74:210–221.
Journal cover image

Published In

Free radical biology & medicine

DOI

EISSN

1873-4596

ISSN

0891-5849

Publication Date

September 2014

Volume

74

Start / End Page

210 / 221

Related Subject Headings

  • Triazoles
  • Semicarbazones
  • Rats, Wistar
  • Rats
  • Oxidative Stress
  • Myocytes, Cardiac
  • Mitochondria, Heart
  • Membrane Potential, Mitochondrial
  • Isonicotinic Acids
  • Iron Chelating Agents