Abstract
Amiodarone (AM) is an efficacious antidysrhythmic agent that is limited clinically by numerous adverse effects. Of greatest concern is AM-induced pulmonary toxicity (AIPT) due to the potential for mortality. Mitochondrial alterations and free radicals have been implicated in the etiology of AM-induced toxicities, including AIPT. Isolated hamster lung and liver mitochondria were assessed for AM-induced effects on respiration, membrane potential, and lipid peroxidation. AM (50–400 μM) stimulated state 4 (resting) respiration at complexes I and II of tightly coupled lung mitochondria, with higher concentrations (200 and 400 μM) resulting in a subsequent inhibition. This biphasic effect of AM (200 μM) was also observed with isolated liver mitochondria. Only inhibition of respiration was observed with AM (50–400 μM) in less tightly coupled lung mitochondria. Based on safranine fluorescence, 200 μM AM decreased lung mitochondrial membrane potential ( p<0.05), while a concentration-dependent (50–200 μM) decrease of membrane potential was observed with liver mitochondria exposed to AM ( p<0.05). Formation of thiobarbituric acid-reactive substances (TBARS) was not altered by AM (50–400 μM) in incubations lasting up to 1 h. These results indicate that lipid peroxidation, as indicated by levels of TBARS, does not play a role in AM-induced alterations in mitochondrial respiration and membrane potential.
Published Version
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