Comparison of various iron chelators and prochelators as protective agents against cardiomyocyte oxidative injury
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu srovnávací studie, časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
R01 GM084176
NIGMS NIH HHS - United States
GM084176
NIGMS NIH HHS - United States
PubMed
24992833
PubMed Central
PMC4243170
DOI
10.1016/j.freeradbiomed.2014.06.019
PII: S0891-5849(14)00271-8
Knihovny.cz E-zdroje
- Klíčová slova
- BSIH, Deferasirox, Free radicals, ICL670A, Iron chelation, Prochelator, Salicylaldehyde isonicotinoyl hydrazone,
- MeSH
- aldehydy chemie farmakologie MeSH
- apoptóza účinky léků MeSH
- benzoáty chemie farmakologie MeSH
- buněčné linie MeSH
- chelátory železa chemie farmakologie MeSH
- cytoprotekce * MeSH
- deferasirox MeSH
- hydrazony chemie farmakologie MeSH
- kardiomyocyty účinky léků fyziologie MeSH
- krysa rodu Rattus MeSH
- kyseliny boronové chemie farmakologie MeSH
- kyseliny isonikotinové chemie farmakologie MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- oxidační stres účinky léků MeSH
- permeabilita buněčné membrány účinky léků MeSH
- peroxid vodíku metabolismus MeSH
- potkani Wistar MeSH
- semikarbazony chemie farmakologie MeSH
- sloučeniny boru chemie farmakologie MeSH
- srdeční mitochondrie účinky léků fyziologie MeSH
- triazoly chemie farmakologie MeSH
- železo chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- srovnávací studie MeSH
- Názvy látek
- (isonicotinic acid (2-(4,4,5,5-tetramethyl-(1,3,2)dioxaborolan-2-yl)benzylidene)hydrazide) MeSH Prohlížeč
- aldehydy MeSH
- benzoáty MeSH
- chelátory železa MeSH
- deferasirox MeSH
- hydrazony MeSH
- kyseliny boronové MeSH
- kyseliny isonikotinové MeSH
- N'-(1-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyloxy)phenyl)ethylidene)isonicotinohydrazide MeSH Prohlížeč
- peroxid vodíku MeSH
- salicylaldehyde isonicotinoyl hydrazone MeSH Prohlížeč
- semikarbazony MeSH
- sloučeniny boru MeSH
- triazoly MeSH
- železo MeSH
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.
Department of Chemistry Duke University Durham NC 22708 USA
Faculty of Pharmacy Charles University Prague 500 05 Hradec Králové Czech Republic
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