title: Amiodarone protects cardiac myocytes against oxidative injury by its free radical scavenging action.
abstract: BACKGROUND
  Oxidative stress plays an important role in the pathophysiology of ischemic heart disease and heart failure, and antioxidants might be beneficial in the treatment of these patients. This study was performed to determine the scavenging effects of amiodarone on oxygen free radicals and its protective effects against oxygen radical-mediated injury in cardiac myocytes.
  
  
  RESULTS
  The formation of the radical spin adduct with hydroxy radical (.OH) in the presence of H(2)O(2) (10 mmol/L) and Fe(3+)-nitrilotriacetate (20 micromol/L) was monitored by electron paramagnetic resonance spectroscopy combined with a spin trapping agent, 5,5-dimethyl pyrroline-N-oxide (DMPO). Amiodarone decreased the intensity of the DMPO-OH signals in a dose-dependent manner (0.1 to 100 micromol/L), whereas other antiarrhythmia drugs such as disopyramide and atenolol had no such effects. Furthermore, amiodarone (10 micromol/L) protected intact adult canine cardiac myocytes against.OH-mediated myocyte injury, as assessed by the degree of morphological change from rod shape to the irreversible hypercontracture state during the exposure of cells to H(2)O(2) and Fe(3+) in vitro.
  
  
  CONCLUSIONS
  Amiodarone can protect cardiac myocytes against oxidative stress-mediated injury by directly scavenging oxygen free radicals. Antioxidant action of amiodarone might potentially contribute to the beneficial effects of this drug in the treatment of patients with ischemic heart disease and congestive heart failure.
authors.affiliation: Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ide
authors.forename: H
authors.initials: H
authors.lastname: Tsutsui
authors.forename: S
authors.initials: S
authors.lastname: Kinugawa
authors.forename: H
authors.initials: H
authors.lastname: Utsumi
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000032:analysis; D004285:Dogs; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D013113:Spin Labels; D019097:Spin Trapping
chemical_list: D000889:Anti-Arrhythmia Agents; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D013113:Spin Labels; C069977:2,2-dimethyl-5-hydroxy-1-pyrrolidinyloxy; D000638:Amiodarone