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Titolo:
Bile acids affect liver mitochondrial bioenergetics: Possible relevance for cholestasis therapy
Autore:
Rolo, AP; Oliveira, PJ; Moreno, AJM; Palmeira, CM;
Indirizzi:
Univ Coimbra, Dept Zool, Ctr Neurosci & Cell Biol Coimbra, P-3004517 Coimbra, Portugal Univ Coimbra Coimbra Portugal P-3004517 bra, P-3004517 Coimbra, Portugal
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 1, volume: 57, anno: 2000,
pagine: 177 - 185
SICI:
1096-6080(200009)57:1<177:BAALMB>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
MEMBRANE-PERMEABILITY TRANSITION; ELECTRON-TRANSPORT CHAIN; ISOLATED RAT HEPATOCYTES; CYCLOSPORINE-A; DUCT LIGATION; MECHANISM; TOXICITY; GLYCOCHENODEOXYCHOLATE; INDUCTION; BALANCE;
Keywords:
mitochondria; bile acids; permeability transition pore; membrane potential; respiration;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Palmeira, CM Univ Coimbra, Dept Zool, Ctr Neurosci & Cell Biol Coimbra, P-3004517 Coimbra, Portugal Univ Coimbra Coimbra Portugal P-3004517 7 Coimbra, Portugal
Citazione:
A.P. Rolo et al., "Bile acids affect liver mitochondrial bioenergetics: Possible relevance for cholestasis therapy", TOXICOL SCI, 57(1), 2000, pp. 177-185

Abstract

It has been pointed out that intracellular accumulation of bile acids cause hepatocyte injury in cholestatic disease process. This study was aimed totest if cytotoxicity of these compounds is mediated through mitochondria dysfunction. Bile acids effects on isolated rat liver mitochondrial were analyzed by monitoring changes in membrane potential and mitochondrial respiration, as well as alterations in H+ membrane permeability and mitochondrial permeability transition pore induction. Increasing concentrations of the bile acids litocholic (LCA), deoxycholic (DCA), ursodeoxycholic (UDCA), chenodeoxycholic (CDCA), glycochenodeoxycholic (GCDC), or taurochenodeoxycholic (TCDC) decrease transmembrane potential (Delta Psi) developed upon succinate energization. These compounds also decreased state 3 respiration and enhanced state 4. We have also demonstrated that the observed concentration-dependent stimulation of state 4 by LCA, DCA, CDCA, TCDC, and GCDC, is associated with an enhanced permeability of mitochondria to H+. Addition of LCA, DCA, CDCA, TCDC, GCDC, and UDCA to mitochondria energized with succinate resulted in a dose-dependent membrane depolarization and stimulation of mitochondrial permeability transition. Tauroursodeoxycholate (TUDC) elicited no significant effect on succinate-supported mitochondrial bioenergetics. In contrast, in the presence of glycoursodeoxycholic (GUDC), Delta Psi increasesas a function of bile salt concentration. The results of this investigation demonstrate that at toxicologically relevant concentrations, most but notall bile acids alter mitochondrial bioenergetics, so impairment of mitochondrial function can be clinically relevant for patients with cholestasis.

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Documento generato il 18/01/20 alle ore 07:36:34