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Characterization of cytoprotective and toxic properties of iron chelator SIH, prochelator BSIH and their degradation products.

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

Free cellular iron catalyzes the formation of toxic hydroxyl radicals and therefore chelation of iron could be a promising therapeutic approach in pathological states associated with oxidative stress. Salicylaldehyde isonicotinoyl hydrazone (SIH) is a strong intracellular iron chelator with well documented potential to protect against oxidative damage both in vitro and in vivo. Due to the short biological half-life of SIH and risk of toxicity due to iron depletion, boronate prochelator BSIH has been designed. BSIH cannot bind iron until it is activated by certain reactive oxygen species to active chelator SIH. The aim of this study was to examine the toxicity and cytoprotective potential of BSIH, SIH, and their decomposition products against hydrogen peroxide-induced injury of H9c2 cardiomyoblast cells. Using HPLC, we observed that salicylaldehyde was the main decomposition products of SIH and BSIH, although a small amount of salicylic acid was also detected. In the case of BSIH, the concentration of formed salicylaldehyde consistently exceeded that of SIH. Isoniazid and salicylic acid were not toxic nor did they provide any antioxidant protective effect in H9c2 cells. In contrast, salicylaldehyde was able to chelate intracellular iron and significantly preserve cellular viability and mitochondrial inner membrane potential induced by hydrogen peroxide. However it was consistently less effective than SIH. The inherent toxicities of salicylaldehyde and SIH were similar. Hence, although SIH - the active chelating agent formed following the BSIH activation - undergoes rapid hydrolysis, its principal decomposition product salicylaldehyde accounts markedly for both cytoprotective and toxic properties.

Duke Scholars

Published In

Toxicology

DOI

EISSN

1879-3185

ISSN

0300-483X

Publication Date

March 2016

Volume

350-352

Start / End Page

15 / 24

Related Subject Headings

  • Toxicology
  • Reactive Oxygen Species
  • Rats
  • Oxidative Stress
  • Myoblasts, Cardiac
  • Membrane Potential, Mitochondrial
  • Isonicotinic Acids
  • Iron Chelating Agents
  • Iron
  • Hydrogen Peroxide
 

Citation

APA
Chicago
ICMJE
MLA
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Jansová, H., Bureš, J., Macháček, M., Hašková, P., Jirkovská, A., Roh, J., … Šimůnek, T. (2016). Characterization of cytoprotective and toxic properties of iron chelator SIH, prochelator BSIH and their degradation products. Toxicology, 350352, 15–24. https://doi.org/10.1016/j.tox.2016.03.004
Jansová, Hana, Jan Bureš, Miloslav Macháček, Pavlína Hašková, Anna Jirkovská, Jaroslav Roh, Qin Wang, Katherine J. Franz, Petra Kovaříková, and Tomáš Šimůnek. “Characterization of cytoprotective and toxic properties of iron chelator SIH, prochelator BSIH and their degradation products.Toxicology 350–352 (March 2016): 15–24. https://doi.org/10.1016/j.tox.2016.03.004.
Jansová H, Bureš J, Macháček M, Hašková P, Jirkovská A, Roh J, et al. Characterization of cytoprotective and toxic properties of iron chelator SIH, prochelator BSIH and their degradation products. Toxicology. 2016 Mar;350–352:15–24.
Jansová, Hana, et al. “Characterization of cytoprotective and toxic properties of iron chelator SIH, prochelator BSIH and their degradation products.Toxicology, vol. 350–352, Mar. 2016, pp. 15–24. Epmc, doi:10.1016/j.tox.2016.03.004.
Jansová H, Bureš J, Macháček M, Hašková P, Jirkovská A, Roh J, Wang Q, Franz KJ, Kovaříková P, Šimůnek T. Characterization of cytoprotective and toxic properties of iron chelator SIH, prochelator BSIH and their degradation products. Toxicology. 2016 Mar;350–352:15–24.
Journal cover image

Published In

Toxicology

DOI

EISSN

1879-3185

ISSN

0300-483X

Publication Date

March 2016

Volume

350-352

Start / End Page

15 / 24

Related Subject Headings

  • Toxicology
  • Reactive Oxygen Species
  • Rats
  • Oxidative Stress
  • Myoblasts, Cardiac
  • Membrane Potential, Mitochondrial
  • Isonicotinic Acids
  • Iron Chelating Agents
  • Iron
  • Hydrogen Peroxide