Cardioprotective effects of iron chelator HAPI and ROS-activated boronate prochelator BHAPI against catecholamine-induced oxidative cellular injury
| Autor: | Tomáš Šimůnek, Miloslav Machacek, Katherine J. Franz, Anna Jirkovská, Jan Bures, Petra Kovaříková, Pavlína Hašková, Hana Jansová |
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| Rok vydání: | 2016 |
| Předmět: |
Boron Compounds
0301 basic medicine Cardiotonic Agents Epinephrine Iron Oxidative phosphorylation 030204 cardiovascular system & hematology Iron Chelating Agents Toxicology medicine.disease_cause Article Cell Line 03 medical and health sciences chemistry.chemical_compound Catecholamines 0302 clinical medicine medicine Animals Humans Prodrugs Chelation Membrane Potential Mitochondrial Semicarbazones Cardioprotection chemistry.chemical_classification Reactive oxygen species Hydroxyl Radical Isoproterenol Glutathione Boronic Acids Rats Oxidative Stress 030104 developmental biology chemistry Biochemistry Biocatalysis Hydroxyl radical Reactive Oxygen Species Oxidative stress Intracellular |
| Zdroj: | Toxicology. 371:17-28 |
| ISSN: | 0300-483X |
| DOI: | 10.1016/j.tox.2016.10.004 |
| Popis: | Catecholamines may undergo iron-promoted oxidation resulting in formation of reactive intermediates (aminochromes) capable of redox cycling and reactive oxygen species (ROS) formation. Both of them induce oxidative stress resulting in cellular damage and death. Iron chelation has been recently shown as a suitable tool of cardioprotection with considerable potential to protect cardiac cells against catecholamine-induced cardiotoxicity. However, prolonged exposure of cells to classical chelators may interfere with physiological iron homeostasis. Prochelators represent a more advanced approach to decrease oxidative injury by forming a chelating agent only under the disease-specific conditions associated with oxidative stress. Novel prochelator (lacking any iron chelating properties) BHAPI [(E)-N′-(1-(2-((4-(4,4,5,5-tetramethyl-1,2,3-dioxoborolan-2-yl)benzyl)oxy)phenyl)ethylidene) isonicotinohydrazide] is converted by ROS to active chelator HAPI with strong iron binding capacity that efficiently inhibits iron-catalyzed hydroxyl radical generation. Our results confirmed redox activity of oxidation products of catecholamines isoprenaline and epinephrine, that were able to activate BHAPI to HAPI that chelates iron ions inside H9c2 cardiomyoblasts. Both HAPI and BHAPI were able to efficiently protect the cells against intracellular ROS formation, depletion of reduced glutathione and toxicity induced by catecholamines and their oxidation products. Hence, both HAPI and BHAPI have shown considerable potential to protect cardiac cells by both inhibition of deleterious catecholamine oxidation to reactive intermediates and prevention of ROS-mediated cardiotoxicity. |
| Databáze: | OpenAIRE |
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