The novel iron chelator, 2-pyridylcarboxaldehyde 2-thiophenecarboxyl hydrazone, reduces catecholamine-mediated myocardial toxicity
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19172757
DOI
10.1021/tx800331j
Knihovny.cz E-resources
- MeSH
- Cell Line MeSH
- Iron Chelating Agents pharmacology MeSH
- Deferoxamine administration & dosage MeSH
- Isoproterenol antagonists & inhibitors metabolism toxicity MeSH
- Myocytes, Cardiac drug effects metabolism MeSH
- Catecholamines antagonists & inhibitors metabolism toxicity MeSH
- Rats MeSH
- Oxidation-Reduction MeSH
- Rats, Wistar MeSH
- Thiophenes pharmacology MeSH
- Iron metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 2-pyridylcarboxaldehyde 2-thiophenecarboxyl hydrazone MeSH Browser
- Iron Chelating Agents MeSH
- Deferoxamine MeSH
- Isoproterenol MeSH
- Catecholamines MeSH
- Thiophenes MeSH
- Iron MeSH
Iron (Fe) chelators are used clinically for the treatment of Fe overload disease. Iron also plays a role in the pathology of many other conditions, and these potentially include the cardiotoxicity induced by catecholamines such as isoprenaline (ISO). The current study examined the potential of Fe chelators to prevent ISO cardiotoxicity. This was done as like other catecholamines, ISO contains the classical catechol moiety that binds Fe and may form redox-active and cytotoxic Fe complexes. Studies in vitro used the cardiomyocyte cell line, H9c2, which was treated with ISO in the presence or absence of the chelator, desferrioxamine (DFO), or the lipophilic ligand, 2-pyridylcarboxaldehyde 2-thiophenecarboxyl hydrazone (PCTH). Both of these chelators were not cardiotoxic and significantly reduced ISO cardiotoxicity in vitro. However, PCTH was far more effective than DFO, with the latter showing activity only at a high, clinically unachievable concentration. Further studies in vitro showed that interaction of ISO with Fe(II)/(III) did not increase cytotoxic radical generation, suggesting that this mechanism was not involved. Studies in vivo were initiated using rats pretreated intravenously with DFO or PCTH before subcutaneous administration of ISO (100 mg/kg). DFO at a clinically used dose (50 mg/kg) failed to reduce catecholamine cardiotoxicity, while PCTH at an equimolar dose totally prevented catecholamine-induced mortality and reduced cardiotoxicity. This study demonstrates that PCTH reduced ISO-induced cardiotoxicity in vitro and in vivo, demonstrating that Fe plays a role, in part, in the pathology observed.
References provided by Crossref.org
Comprehensive review of cardiovascular toxicity of drugs and related agents
Protective Effects of D-Penicillamine on Catecholamine-Induced Myocardial Injury
