Cardiac-specific overexpression of tumor necrosis factor-alpha significantly increased myocardial production of hydroxyl radicals, likely originating from damaged myocytes rather than inflammatory cells.
Does cyclophosphamide treatment reduce myocardial production of hydroxyl radical in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-alpha?
In a murine model of TNF-alpha-induced cardiomyopathy, reactive oxygen species appear to originate from damaged myocytes rather than infiltrating inflammatory cells.
Transgenic (TG) mice with cardiac-specific overexpression of tumor necrosis factor-alpha develop congestive heart failure with myocardial inflammation. The purpose of this study was to investigate the effects of tumor necrosis factor-alpha on reactive oxygen species (ROS) in this mouse model of cardiomyopathy. Myocardial production of hydroxyl radical detected by electron spin resonance spectroscopy was significantly increased in TG. Myocardial expression of Mn-SOD was significantly decreased in TG, whereas that of Cu,Zn-SOD was unaltered. Myocardial expression of catalase was unchanged, whereas that of glutathione peroxidase was significantly increased, in TG. Histological analysis revealed that macrophages and CD4-positive lymphocytes were increased in TG myocardium. To investigate whether these infiltrating inflammatory cells were the source of ROS, we treated TG mice with cyclophosphamide for 7 days. Although cyclophosphamide significantly suppressed the infiltration of inflammatory cells, it did not diminish the production of hydroxyl radical in TG myocardium. Damaged myocytes, but not infiltrating inflammatory cells, may be the source of ROS in TG.
Machida et al. (Sat,) conducted a other in Cardiomyopathy. Cardiac-specific overexpression of tumor necrosis factor-alpha vs. Non-transgenic controls (implied) was evaluated on Myocardial production of hydroxyl radical. Cardiac-specific overexpression of tumor necrosis factor-alpha significantly increased myocardial production of hydroxyl radicals, likely originating from damaged myocytes rather than inflammatory cells.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: