Apocynin attenuates isoproterenol-induced myocardial injury and fibrogenesis

• Published in: Biochemical and biophysical research communications 2014-06, Vol.449 (1), p.55-61
• Main Authors: Liu, Li, Cui, Jingang, Yang, Qinbo, Jia, Chenglin, Xiong, Minqi, Ning, Bingbing, Du, Xiaoye, Wang, Peiwei, Yu, Xintong, Li, Li, Wang, Wenjian, Chen, Yu, Zhang, Teng
• Format: Article
• Language: English
• Subjects: Acetophenones - administration & dosage; Animals; Antioxidants - administration & dosage; Apocynin; Cardiomyopathies - chemically induced; Cardiomyopathies - drug therapy; Cardiomyopathies - metabolism; Female; Fibrosis; Fibrosis - chemically induced; Fibrosis - drug therapy; Fibrosis - metabolism; Gene expression; Humans; Isoproterenol; Male; Mice; Mice, Inbred C57BL; Myocardial injury; Oxidative Stress - drug effects; Reactive oxygen species; Reactive Oxygen Species - metabolism; Treatment Outcome
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.04.157

•Apocynin attenuated the development of ISO-induced myocardial injury and fibrosis in the mouse.•Apocynin suppressed NADPH oxidase-mediated ROS generation in ISO-challenged mouse heart.•Apocynin decreased the expression of genes implicated in inflammatory response.•Apocynin decreased the expression of genes implicated in fibrogenic response. Oxidative stress is mechanistically implicated in the pathogenesis of myocardial injury and the subsequent fibrogenic tissue remodeling. Therapies targeting oxidative stress in the process of myocardial fibrogenesis are still lacking and thus remain as an active research area in myocardial injury management. The current study evaluated the effects of a NADPH oxidase inhibitor, apocynin, on the production of reactive oxygen species and the development of myocardial fibrogenesis in isoproterenol (ISO)-induced myocardial injury mouse model. The results revealed a remarkable effect of apocynin on attenuating the development of myocardial necrotic lesions, inflammation and fibrogenesis. Additionally, the protective effects of apocynin against myocardial injuries were associated with suppressed expression of an array of genes implicated in inflammatory and fibrogenic responses. Our study thus provided for the first time the histopathological and molecular evidence supporting the therapeutic value of apocynin against the development of myocardial injuries, in particular, myocardial fibrogenesis, which will benefit the mechanism-based drug development targeting oxidative stress in preventing and/or treating related myocardial disorders.