Cardioprotective Potential of Iron Chelators and Prochelators

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F19%3A10399965" target="_blank" >RIV/00216208:11160/19:10399965 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=o_GG9kk0RY" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=o_GG9kk0RY</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/0929867324666170920155439" target="_blank" >10.2174/0929867324666170920155439</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cardioprotective Potential of Iron Chelators and Prochelators

Popis výsledku v původním jazyce

Heart is a particularly sensitive organ to iron overload and cardiomyopathy due to the excessive cardiac iron deposition causes most deaths in disorders such as beta-thalassemia major. Free or loosely bound iron ions readily cycle between ferrous and ferric states and catalyze Haber-Weiss reaction that yields highly reactive and toxic hydroxyl radicals. Treatment with iron chelators (desferrioxamine, deferiprone, and deferasirox) substantially improved cardiovascular morbidity and mortality in iron overloaded patients. Furthermore, iron chelators have been studied in various cardiovascular disorders with known or presumed oxidative stress roles (e.g., ischemia/reperfusion injury) also in patients with normal body iron contents. The pharmacodynamic and pharmacokinetic properties of these chelators are critical for effective therapy. For example, the widely clinically used but hydrophilic chelator desferrioxamine suffers from poor plasma membrane permeability, which means that high and clinically unachievable concentrations/doses must be employed to obtain cardioprotection. Therefore, small-molecular and lipophilic chelators with oral availability are more suitable for this purpose, particularly in states without systemic iron overload, Apart from agents that are already used in clinical practice, aroylhydrazone iron chelators, namely salicylaldehyde isonicotinoyl hydrazone (SIH), have provided promising results. However, the use of classical iron-chelating agents is associated with a risk of toxicity due to indiscriminate iron depletion. Recent studies have therefore focused on &quot;masked&quot; prochelators that have little or no affinity for iron until site-specific activation by reactive oxygen species.

Název v anglickém jazyce

Cardioprotective Potential of Iron Chelators and Prochelators

Popis výsledku anglicky

Heart is a particularly sensitive organ to iron overload and cardiomyopathy due to the excessive cardiac iron deposition causes most deaths in disorders such as beta-thalassemia major. Free or loosely bound iron ions readily cycle between ferrous and ferric states and catalyze Haber-Weiss reaction that yields highly reactive and toxic hydroxyl radicals. Treatment with iron chelators (desferrioxamine, deferiprone, and deferasirox) substantially improved cardiovascular morbidity and mortality in iron overloaded patients. Furthermore, iron chelators have been studied in various cardiovascular disorders with known or presumed oxidative stress roles (e.g., ischemia/reperfusion injury) also in patients with normal body iron contents. The pharmacodynamic and pharmacokinetic properties of these chelators are critical for effective therapy. For example, the widely clinically used but hydrophilic chelator desferrioxamine suffers from poor plasma membrane permeability, which means that high and clinically unachievable concentrations/doses must be employed to obtain cardioprotection. Therefore, small-molecular and lipophilic chelators with oral availability are more suitable for this purpose, particularly in states without systemic iron overload, Apart from agents that are already used in clinical practice, aroylhydrazone iron chelators, namely salicylaldehyde isonicotinoyl hydrazone (SIH), have provided promising results. However, the use of classical iron-chelating agents is associated with a risk of toxicity due to indiscriminate iron depletion. Recent studies have therefore focused on &quot;masked&quot; prochelators that have little or no affinity for iron until site-specific activation by reactive oxygen species.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/GA13-15008S" target="_blank" >GA13-15008S: Nová potenciální kardioprotektiva: studium vztahů mezi chemickou strukturou a protektivním účinkem u různých typů poškození myokardu</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Current Medicinal Chemistry

ISSN

0929-8673

e-ISSN

—

Svazek periodika

26

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

14

Strana od-do

288-301

Kód UT WoS článku

000461143200006

EID výsledku v databázi Scopus

2-s2.0-85063712756