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Cardioprotective effects of iron chelator HAPI and ROS-activated boronate prochelator BHAPI against catecholamine-induced oxidative cellular injury.

Publication ,  Journal Article
Hašková, P; Jansová, H; Bureš, J; Macháček, M; Jirkovská, A; Franz, KJ; Kovaříková, P; Šimůnek, T
Published in: Toxicology
September 2016

Catecholamines may undergo iron-promoted oxidation resulting in formation of reactive intermediates (aminochromes) capable of redox cycling and reactive oxygen species (ROS) formation. Both of them induce oxidative stress resulting in cellular damage and death. Iron chelation has been recently shown as a suitable tool of cardioprotection with considerable potential to protect cardiac cells against catecholamine-induced cardiotoxicity. However, prolonged exposure of cells to classical chelators may interfere with physiological iron homeostasis. Prochelators represent a more advanced approach to decrease oxidative injury by forming a chelating agent only under the disease-specific conditions associated with oxidative stress. Novel prochelator (lacking any iron chelating properties) BHAPI [(E)-Ń-(1-(2-((4-(4,4,5,5-tetramethyl-1,2,3-dioxoborolan-2-yl)benzyl)oxy)phenyl)ethylidene) isonicotinohydrazide] is converted by ROS to active chelator HAPI with strong iron binding capacity that efficiently inhibits iron-catalyzed hydroxyl radical generation. Our results confirmed redox activity of oxidation products of catecholamines isoprenaline and epinephrine, that were able to activate BHAPI to HAPI that chelates iron ions inside H9c2 cardiomyoblasts. Both HAPI and BHAPI were able to efficiently protect the cells against intracellular ROS formation, depletion of reduced glutathione and toxicity induced by catecholamines and their oxidation products. Hence, both HAPI and BHAPI have shown considerable potential to protect cardiac cells by both inhibition of deleterious catecholamine oxidation to reactive intermediates and prevention of ROS-mediated cardiotoxicity.

Duke Scholars

Published In

Toxicology

DOI

EISSN

1879-3185

ISSN

0300-483X

Publication Date

September 2016

Volume

371

Start / End Page

17 / 28

Related Subject Headings

  • Toxicology
  • Semicarbazones
  • Reactive Oxygen Species
  • Rats
  • Prodrugs
  • Oxidative Stress
  • Membrane Potential, Mitochondrial
  • Isoproterenol
  • Iron Chelating Agents
  • Iron
 

Citation

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Hašková, P., Jansová, H., Bureš, J., Macháček, M., Jirkovská, A., Franz, K. J., … Šimůnek, T. (2016). Cardioprotective effects of iron chelator HAPI and ROS-activated boronate prochelator BHAPI against catecholamine-induced oxidative cellular injury. Toxicology, 371, 17–28. https://doi.org/10.1016/j.tox.2016.10.004
Hašková, Pavlína, Hana Jansová, Jan Bureš, Miloslav Macháček, Anna Jirkovská, Katherine J. Franz, Petra Kovaříková, and Tomáš Šimůnek. “Cardioprotective effects of iron chelator HAPI and ROS-activated boronate prochelator BHAPI against catecholamine-induced oxidative cellular injury.Toxicology 371 (September 2016): 17–28. https://doi.org/10.1016/j.tox.2016.10.004.
Hašková P, Jansová H, Bureš J, Macháček M, Jirkovská A, Franz KJ, et al. Cardioprotective effects of iron chelator HAPI and ROS-activated boronate prochelator BHAPI against catecholamine-induced oxidative cellular injury. Toxicology. 2016 Sep;371:17–28.
Hašková, Pavlína, et al. “Cardioprotective effects of iron chelator HAPI and ROS-activated boronate prochelator BHAPI against catecholamine-induced oxidative cellular injury.Toxicology, vol. 371, Sept. 2016, pp. 17–28. Epmc, doi:10.1016/j.tox.2016.10.004.
Hašková P, Jansová H, Bureš J, Macháček M, Jirkovská A, Franz KJ, Kovaříková P, Šimůnek T. Cardioprotective effects of iron chelator HAPI and ROS-activated boronate prochelator BHAPI against catecholamine-induced oxidative cellular injury. Toxicology. 2016 Sep;371:17–28.
Journal cover image

Published In

Toxicology

DOI

EISSN

1879-3185

ISSN

0300-483X

Publication Date

September 2016

Volume

371

Start / End Page

17 / 28

Related Subject Headings

  • Toxicology
  • Semicarbazones
  • Reactive Oxygen Species
  • Rats
  • Prodrugs
  • Oxidative Stress
  • Membrane Potential, Mitochondrial
  • Isoproterenol
  • Iron Chelating Agents
  • Iron