Amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice

Journal Article · Sat Dec 01 04:00:00 EST 1990 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:6249494

Fromenty, B; Fisch, C; Labbe, G; Degott, C; Deschamps, D; Berson, A; Letteron, P; Pessayre, D ^[1]

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1. Institut National de la Sante et de la Recherche Medicale U24, Clichy (France)

Amiodarone has been shown to produce microvesicular steatosis of the liver in some recipients. We have determined the effects of amiodarone on the mitochondrial oxidation of fatty acids in mice. In vitro, the formation of 14C-acid-soluble beta-oxidation products from (U-14C)palmitic acid by mouse liver mitochondria was decreased by 92% in the presence of 125 microM amiodarone and by 94% in the presence of 125 microM N-desethylamiodarone. Inhibition due to 100 or 150 microM amiodarone persisted in the presence of 5 mM acetoacetate, whereas acetoacetate totally relieved inhibition due to 15 microM rotenone. In vivo, exhalation of (14C)CO2 from (U-14C)palmitic acid was decreased by 31, 40, 58 and 78%, respectively, in mice receiving 19, 25, 50 and 100 mg.kg-1 of amiodarone hydrochloride 1 hr before the administration of (U-14C)palmitic acid. One hour after 100 mg.kg-1, the exhalation of (14C)CO2 from (1-14C)palmitic acid, (1-14C)octanoic acid or (1-14C)butyric acid was decreased by 78, 72 and 53%, respectively. Exhalation of (14C)CO2 from (1-14C)palmitic acid was normal between 6 and 9 hr after administration of 100 mg.kg-1 of amiodarone hydrochloride, but was still inhibited by 71 and 37%, 24 and 48 hr after 600 mg.kg-1. Twenty four hours after the latter dose of amiodarone, hepatic triglycerides were increased by 150%, and there was microvesicular steatosis of the liver. We conclude that amiodarone inhibits the mitochondrial beta-oxidation of fatty acids and produces microvesicular steatosis of the liver in mice.

• OSTI ID: 6249494
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Journal Name: Journal of Pharmacology and Experimental Therapeutics; (USA) Vol. 255:3; ISSN 0022-3565; ISSN JPETA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BIOLOGICAL EFFECTS
BODY
CARBON 14 COMPOUNDS
CARBON COMPOUNDS
CARBON DIOXIDE
CARBON OXIDES
CARBOXYLIC ACIDS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CHALCOGENIDES
CHEMICAL REACTIONS
DIGESTIVE SYSTEM
DIGESTIVE SYSTEM DISEASES
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
GLANDS
HEXADECANOIC ACID
INHIBITION
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
MAMMALS
METABOLISM
MICE
MITOCHONDRIA
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
PATHOGENESIS
REDOX REACTIONS
RODENTS
TRACER TECHNIQUES
VASODILATORS
VERTEBRATES