AMIODARONE-INDUCED DISRUPTION OF HAMSTER LUNG AND LIVER MITOCHONDRIAL-FUNCTION - LACK OF ASSOCIATION WITH THIOBARBITURIC ACID-REACTIVE SUBSTANCE PRODUCTION

Amiodarone (AM) is an efficacious antidysrhythmic agent that is limite d clinically by numerous adverse effects. Of greatest concern is AM-in duced pulmonary toxicity (AIPT) due to the potential for mortality. Mi tochondrial alterations and free radicals have been implicated in the etiology of AM-induced toxicities, including AIPT. Isolated hamster lu ng and liver mitochondria were assessed for AM-induced effects on resp iration, membrane potential, and lipid peroxidation. AM (50-400 mu M) stimulated state 4 (resting) respiration at complexes I and II of tigh tly coupled lung mitochondria, with higher concentrations (200 and 400 mu M) resulting in a subsequent inhibition. This biphasic effect of A M (200 mu M) was also observed with isolated liver mitochondria. Only inhibition of respiration was observed with AM (50-400 mu M) in less t ightly coupled lung mitochondria. Based on safranine fluorescence, 200 mu M decreased lung mitochondrial membrane potential (p < 0.05), whil e a concentration-dependent (50-200 mu M) decrease of membrane potenti al was observed with liver mitochondria exposed to AM (p < 0.05). Form ation of thiobarbituric acid-reactive substances (TBARS) was not alter ed by AM (50-400 mu M) in incubations lasting up to 1 h. These results indicate that lipid peroxidation, as indicated by levels of TEARS, do es not play a role in AM-induced alterations in mitochondrial respirat ion and membrane potential. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.