EFFECT OF AMIODARONE (AMD) ON THE ANTIOXIDANT ENZYMES, LIPID-PEROXIDATION AND MITOCHONDRIAL METABOLISM

The effects of amiodarone (AMD) on lipid peroxidation of rat liver mit ochondria, the formation of superoxide anions at the respiratory chain level, and the cytosolic and mitochondrial enzymatic protective mecha nisms of oxidative stress were studied. An attempt of classify AMD acc ording to its toxic ability to interfere with the integrated function of electron transport enzymes was also investigated. The results confi rm the effects of AMD on complex I and permit the placing of this drug in class A of the classification of Knobeloch, together with rotenone , amytal and chaotropic agents. AMD has no effect on the activity of t he enzymes superoxide dismutase, catalase, glutathione reductase and g lutathione peroxidase, nor on glucose 6-phosphate dehydrogenase. AMD d id not promote an increase in the formation of anion superoxide at the respiratory chain level. Pre-incubation with AMD (16.6 mu M) inhibite d about 70 per cent of lipid peroxidation. The results suggest a prote ctive effect of AMD against lipid peroxidation in mitochondrial membra nes by iron-dependent systems. (C) 1997 John Wiley & Sons, Ltd.