Iron chelation with salicylaldehyde isonicotinoyl hydrazone protects against catecholamine autoxidation and cardiotoxicity
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21147217
DOI
10.1016/j.freeradbiomed.2010.12.004
PII: S0891-5849(10)01409-7
Knihovny.cz E-resources
- MeSH
- Aldehydes pharmacology MeSH
- Cell Line MeSH
- Iron Chelating Agents pharmacology MeSH
- Cytoprotection MeSH
- Enzyme Assays MeSH
- Hydrazones pharmacology MeSH
- Caspases metabolism MeSH
- Catecholamines metabolism MeSH
- Binding, Competitive MeSH
- Coordination Complexes pharmacology MeSH
- Rats MeSH
- Ascorbic Acid chemistry MeSH
- Myoblasts, Cardiac cytology drug effects metabolism MeSH
- Oxidation-Reduction MeSH
- Oxidative Stress MeSH
- Reactive Oxygen Species metabolism MeSH
- Cell Survival drug effects MeSH
- Iron metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Aldehydes MeSH
- Iron Chelating Agents MeSH
- Hydrazones MeSH
- Caspases MeSH
- Catecholamines MeSH
- Coordination Complexes MeSH
- Ascorbic Acid MeSH
- Reactive Oxygen Species MeSH
- salicylaldehyde isonicotinoyl hydrazone MeSH Browser
- Iron MeSH
Elevated catecholamine levels are known to induce damage of the cardiac tissue. This catecholamine cardiotoxicity may stem from their ability to undergo oxidative conversion to aminochromes and concomitant production of reactive oxygen species (ROS), which damage cardiomyocytes via the iron-catalyzed Fenton-type reaction. This suggests the possibility of cardioprotection by iron chelation. Our in vitro experiments have demonstrated a spontaneous decrease in the concentration of the catecholamines epinephrine and isoprenaline during their 24-h preincubation in buffered solution as well as their gradual conversion to oxidation products. These changes were significantly augmented by addition of iron ions and reduced by the iron-chelating agent salicylaldehyde isonicotinoyl hydrazone (SIH). Oxidized catecholamines were shown to form complexes with iron that had significant redox activity, which could be suppressed by SIH. Experiments using the H9c2 cardiomyoblast cell line revealed higher cytotoxicity of oxidized catecholamines than of the parent compounds, apparently through the induction of caspase-independent cell death, whereas co-incubation of cells with SIH was able to significantly preserve cell viability. A significant increase in intracellular ROS formation was observed after the incubation of cells with catecholamine oxidation products; this could be significantly reduced by SIH. In contrast, parent catecholamines did not increase, but rather decreased, cellular ROS production. Hence, our results demonstrate an important role for redox-active iron in catecholamine autoxidation and subsequent toxicity. The iron chelator SIH has shown considerable potential to protect cardiac cells by both inhibition of deleterious catecholamine oxidation to reactive intermediates and prevention of ROS-mediated cardiotoxicity.
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
