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. Methods and 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 μmol/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 μmol/L), whereas other antiarrhythmia drugs such as disopyramide and atenolol had no such effects. Furthermore, amiodarone (10 μmol/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.

Amiodarone pretreatment of organ donors exerts anti-oxidative protection but induces excretory dysfunction in liver preservation and reperfusion

“…ROS produce deleterious effects on liver cells, including mitochondrial damage 29. In vitro experiments with cardiac myocytes and liver mitochondria have suggested that AM exhibits inhibitory effects against oxygen radical–mediated lipid peroxidation of cardiac and rat liver mitochondria 30, 31. However, in the present study, GLDH, which may serve as an indicator for mitochondrial injury, was not reduced after AM pretreatment.…”

Mitochondrial proteome remodeling in ischemic heart failure

“…Mitochondria are considered both a primary source of ROS, and a target for ROS damage (Ide et al, 2000, Kuroda et al, 2010). ROS are markedly increased in failing myocardium (Belch et al, 1991, Ide et al, 1999, Tsutsui et al, 2001, Tsutsui et al, 2006). The primary source of cardiac ROS appears to be uncoupling of the electron transport chain at the level of complexes I and III, but this has been questioned by some (Brown and Borutaite, 2012, Ide et al, 2001).…”

mitoNEET Regulates Mitochondrial Iron Homeostasis Interacting with Transferrin Receptor

“…Many previous reports have shown that enhanced ROS production leads to cardiac dysfunction and development of heart failure (HF). We previously reported that an exposure of H 2 O 2 to cardiac myocytes lead to their injury (Ide, Tsutsui et al, 1999). Furthermore we reported that mitochondria-derived ROS production was increased in the heart from HF model mice (Kinugawa, Tsutsui et al, 2000), and that the treatment with anti-oxidant and overexpression of mitochondrial antioxidant, such as peroxiredoxin-3, improved cardiac function and HF (Matsushima, Ide et al, 2006).…”