NecroX-7 prevents oxidative stress-induced cardiomyopathy by inhibition of NADPH oxidase activity in rats
| Autor: | Sun Young Koo, Heui Sul Park, Joonghoon Park, Hyo-Shin Kwak, Hyoung Jin Kim, Dong Wook Kim, Ji-Hoon Park, Hyeon Joo Yim, Eok Park, Myoung-Sub Song, Dong Ook Seo, Soon Ha Kim, Bong-Hyun Ahn |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Mitochondrial ROS
Male Cardiotonic Agents Cardiomyopathy Mitochondrion Toxicology medicine.disease_cause Real-Time Polymerase Chain Reaction Cell Line Rats Sprague-Dawley chemistry.chemical_compound tert-Butylhydroperoxide Lactate dehydrogenase medicine Animals Myocytes Cardiac Organic Chemicals Creatine Kinase Pharmacology Cardioprotection NADPH oxidase biology L-Lactate Dehydrogenase NADPH Oxidases Free Radical Scavengers medicine.disease Microarray Analysis Molecular biology Rats Oxidative Stress chemistry Apoptosis Doxorubicin biology.protein Cardiomyopathies Oxidative stress |
| Zdroj: | Toxicology and applied pharmacology. 263(1) |
| ISSN: | 1096-0333 |
| Popis: | Oxidative stress is one of the causes of cardiomyopathy. In the present study, NecroXs, novel class of mitochondrial ROS/RNS scavengers, were evaluated for cardioprotection in in vitro and in vivo model, and the putative mechanism of the cardioprotection of NecroX-7 was investigated by global gene expression profiling and subsequent biochemical analysis. NecroX-7 prevented tert-butyl hydroperoxide (tBHP)-induced death of H9C2 rat cardiomyocytes at EC(50)=0.057 μM. In doxorubicin (DOX)-induced cardiomyopathy in rats, NecroX-7 significantly reduced the plasma levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) which were increased by DOX treatment (p0.05). Microarray analysis revealed that 21 genes differentially expressed in tBHP-treated H9C2 cells were involved in 'Production of reactive oxygen species' (p=0.022), and they were resolved by concurrent NecroX-7 treatment. Gene-to-gene networking also identified that NecroX-7 relieved cell death through Ncf1/p47phox and Rac2 modulation. In subsequent biochemical analysis, NecroX-7 inhibited NADPH oxidase (NOX) activity by 53.3% (p0.001). These findings demonstrate that NecroX-7, in part, provides substantial protection of cardiomyopathy induced by tBHP or DOX via NOX-mediated cell death. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect