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Titolo:
Toxicity of amiodarone and amiodarone analogues on isolated rat liver mitochondria
Autore:
Spaniol, M; Bracher, R; Ha, HR; Follath, F; Krahenbuhl, S;
Indirizzi:
Univ Basel Hosp, Div Clin Pharmacol & Toxicol, CH-4031 Basel, Switzerland Univ Basel Hosp Basel Switzerland CH-4031 ol, CH-4031 Basel, Switzerland Univ Zurich Hosp, Cardiol Res Unit, CH-8091 Zurich, Switzerland Univ Zurich Hosp Zurich Switzerland CH-8091 CH-8091 Zurich, Switzerland
Titolo Testata:
JOURNAL OF HEPATOLOGY
fascicolo: 5, volume: 35, anno: 2001,
pagine: 628 - 636
SICI:
0168-8278(200111)35:5<628:TOAAAA>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
BETA-OXIDATION; COMPLEX-III; HEPATOTOXICITY; INHIBITION; METABOLISM; BENZARONE;
Keywords:
amiodarone; mitochondria; electron transport chain; beta-oxidation; ketogenesis; liver injury;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Krahenbuhl, S Univ Basel Hosp, Div Clin Pharmacol & Toxicol, Petersgraben 4, CH-4031 Basel, Switzerland Univ Basel Hosp Petersgraben 4 Basel Switzerland CH-4031 nd
Citazione:
M. Spaniol et al., "Toxicity of amiodarone and amiodarone analogues on isolated rat liver mitochondria", J HEPATOL, 35(5), 2001, pp. 628-636

Abstract

Background: Amiodarone is a well-known mitochondrial toxin consisting of abenzofuran ring (ring A) coupled to a p-OH-benzene structure substituted with 2 iodines and a diethyl-ethanolamine side chain (ring B). Aim: To find out which part of amiodarone is responsible for mitochondrialtoxicity. Methods: Amiodarone, ring A and B without the ethanolamine side-chain and iodines (B0), ring A and B with iodines but no ethanolamine (B2), ring B with 1 iodine and no ethanolamine (C1) and ring B with ethanolamine and 2 iodines (D2) were studied. Results: In freshly isolated rat liver mitochondria, amiodarone inhibited state 3 glutamate and palmitoyl-CoA oxidation and decreased the respiratorycontrol ratios. B0 and B2 were more potent inhibitors than amiodarone and B2 more potent than B0. C1 and D2 showed no significant mitochondrial toxicity. After disruption, mitochondrial oxidases and complexes of the electrontransport chain were inhibited by amiodarone, B0 and B2, whereas C1 and D2revealed no inhibition. Beta-oxidation showed a strong inhibition by amiodarone, B0 and B2 but not by C1 or D2. Ketogenesis was almost unaffected. Conclusions: Amiodarone, B0 and B2 are uncouplers of oxidative phosphorylation, and inhibit complexes I, II and III, and beta -oxidation. The benzofuran structure is responsible for mitochondrial toxicity of amiodarone and the presence of iodine is not essential. (C) 2001 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 03:43:09