Effect of amiodarone (AMD) on the antioxidant enzymes, lipid peroxidation and mitochondrial metabolism.
The effects of amiodarone (AMD) on lipid peroxidation of rat liver mitochondria, the formation of superoxide anions at the respiratory chain level, and the cytosolic and mitochondrial enzymatic protective mechanisms of oxidative stress were studied. An attempt of classify AMD according to its toxic ability to interfere with the integrated function of electron transport enzymes was also investigated. The results confirm 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 the enzymes superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase, nor on glucose 6-phosphate dehydrogenase. AMD did not promote an increase in the formation of anion superoxide at the respiratory chain level. Pre-incubation with AMD (16.6 microM) inhibited about 70 per cent of lipid peroxidation. The results suggest a protective effect of AMD against lipid peroxidation in mitochondrial membranes by iron-dependent systems.
Ribeiro
S M
SM
Departamento de Bioquímica, Universidade Federal do Paraná, Curitiba, PR., Brazil.
Campello
A P
AP
Nascimento
A J
AJ
Kluppel
M L
ML
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D004579:Electron Transport / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000201:enzymology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D004791:Enzyme Inhibitors; D009249:NADP; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); D005980:Glutathione Reductase; D000638:Amiodarone