Amiodarone-induced disruption of hamster lung and liver mitochondrial function: lack of association with thiobarbituric acid-reactive substance production

• Published in: Toxicology letters Vol. 98; no. 1; pp. 41 - 50
• Main Authors: Card, Jeffrey W, Lalonde, Brendon R, Rafeiro, Elizabeth, Tam, Andrew S, Racz, William J, Brien, James F, Bray, Tammy M, Massey, Thomas E
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01-09-1998; Amsterdam Elsevier Science
• Subjects: Amiodarone; Amiodarone - pharmacology; Animals; Anti-Arrhythmia Agents - pharmacology; Biological and medical sciences; Cricetinae; Drug toxicity and drugs side effects treatment; Lipid peroxidation; Lipid Peroxidation - drug effects; Liver; Lung; Lung - drug effects; Lung - metabolism; Lung - ultrastructure; Male; Medical sciences; Membrane Potentials - drug effects; Mesocricetus; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Oxygen Consumption - drug effects; Pharmacology. Drug treatments; Thiobarbituric Acid Reactive Substances - metabolism; Toxicity: respiratory system, ent, stomatology; Lipid peroxidation; Mitochondria; Amiodarone; Lung; Liver; Antianginal agent; Respiratory disease; Toxicity; Coronary vasodilator agent; Rodentia; Lipids; Antiarrhythmic agent; Iodine Organic compounds; In vitro; Vertebrata; Mammalia; Animal; Digestive diseases; Oxidation; Membrane potential; Mechanism of action; Respiration; Hamster; Peroxidation
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/S0378-4274(98)00097-6

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.