NecroX-7 prevents oxidative stress-induced cardiomyopathy by inhibition of NADPH oxidase activity in rats |
| |
Authors: | Park Joonghoon Park Eok Ahn Bong-Hyun Kim Hyoung Jin Park Ji-hoon Koo Sun Young Kwak Hyo-Shin Park Heui Sul Kim Dong Wook Song Myoungsub Yim Hyeon Joo Seo Dong Ook Kim Soon Ha |
| |
Affiliation: | a LG Life Sciences Ltd., R&D Park, Daejeon, 305-380, Republic of Koreab Department of Biochemistry, School of Medicine, Chungnam National University, Daejeon, 301-747, Republic of Korea |
| |
Abstract: | 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 EC50 = 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 (p < 0.05). 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% (p < 0.001). These findings demonstrate that NecroX-7, in part, provides substantial protection of cardiomyopathy induced by tBHP or DOX via NOX-mediated cell death. |
| |
Keywords: | NecroX-7 Doxorubicin tert-Butyl hydroperoxide NADPH oxidase Cardiomyopathy |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|