Impairment of mitochondrial oxidative phosphorylation in rat fatty liver exposed to preservation-reperfusion injury

Caraceni, Paolo; Bianchi, Cristina; Domenicali, Marco; Maria Pertosa, Anna; Maiolini, Elisabetta; Parenti Castelli, Giovanna; Nardo, Bruno; Trevisani, Franco; Lenaz, Giorgio; Bernardi, Mauro

doi:10.1016/j.jhep.2004.03.022

« Previous Next »Journal of Hepatology
Volume 41, Issue 1 , Pages 82-88, July 2004

Impairment of mitochondrial oxidative phosphorylation in rat fatty liver exposed to preservation-reperfusion injury

Paolo Caraceni
- Dipartimento di Medicina Interna, Cardioangiologia ed Epatologia, University of Bologna, Policlinico Sant'Orsola, Via Massarenti 9, 40138 Bologna, Italy
- Centro Ricerca Biomedica Applicata (C.R.B.A.), University of Bologna, 40138 Bologna, Italy
- Corresponding author. Tel.: +39-51-636-4912; fax: +39-51-340-877
Cristina Bianchi
- Dipartimento di Biochimica, University of Bologna, 40138 Bologna, Italy
Marco Domenicali
- Dipartimento di Medicina Interna, Cardioangiologia ed Epatologia, University of Bologna, Policlinico Sant'Orsola, Via Massarenti 9, 40138 Bologna, Italy
- Centro Ricerca Biomedica Applicata (C.R.B.A.), University of Bologna, 40138 Bologna, Italy
Anna Maria Pertosa
- Dipartimento di Medicina Interna, Cardioangiologia ed Epatologia, University of Bologna, Policlinico Sant'Orsola, Via Massarenti 9, 40138 Bologna, Italy
- Centro Ricerca Biomedica Applicata (C.R.B.A.), University of Bologna, 40138 Bologna, Italy
Elisabetta Maiolini
- Dipartimento di Medicina Interna, Cardioangiologia ed Epatologia, University of Bologna, Policlinico Sant'Orsola, Via Massarenti 9, 40138 Bologna, Italy
Giovanna Parenti Castelli
- Dipartimento di Biochimica, University of Bologna, 40138 Bologna, Italy
Bruno Nardo
- Centro Ricerca Biomedica Applicata (C.R.B.A.), University of Bologna, 40138 Bologna, Italy
- Dipartimento di Scienze Chirurgiche, Rianimatorie e dei Trapianti, University of Bologna, 40138 Bologna, Italy
Franco Trevisani
- Dipartimento di Medicina Interna, Cardioangiologia ed Epatologia, University of Bologna, Policlinico Sant'Orsola, Via Massarenti 9, 40138 Bologna, Italy
Giorgio Lenaz
- Dipartimento di Biochimica, University of Bologna, 40138 Bologna, Italy
Mauro Bernardi
- Dipartimento di Medicina Interna, Cardioangiologia ed Epatologia, University of Bologna, Policlinico Sant'Orsola, Via Massarenti 9, 40138 Bologna, Italy
- Centro Ricerca Biomedica Applicata (C.R.B.A.), University of Bologna, 40138 Bologna, Italy

Received 14 July 2003; received in revised form 12 February 2004; accepted 31 March 2004.

See Editorial, pages 149–151

Abstract

Background/Aims

As the impairment of the cellular energy metabolism contributes to the failure of fatty liver grafts after transplantation, we aimed to determine whether steatosis affects the oxidative phosphorylation activity during preservation.

Methods

Rat normal and fatty livers were preserved for 18 h and then reperfused with warm oxygenated solution. The oxidative phosphorylation, the F₀F₁-ATPase and the Complex I activities were assessed in isolated mitochondria before and after preservation, and during reperfusion. The ALT release and portal pressure were monitored during reperfusion.

Results

The baseline phosphorylation activity was similar in normal and steatotic mitochondria. After cold preservation, the respiratory control index and state 3 respiration decreased significantly only in steatotic livers. Reperfusion induced a further deterioration in either group. Contrary to normal liver, uncoupling of fatty liver mitochondria allowed the recovery of the maximal respiration rate only using succinate (Complex II-dependent substrate), but not glutamate-malate (Complex I-dependent). Complex I dysfunction was confirmed spectrophotometrically. The ATPase activity was also significantly lower in fatty livers. Finally, ALT release and portal pressure were greater in steatotic livers.

Conclusions

The alteration of the oxidative phosphorylation activity during preservation is greatly exacerbated by fatty infiltration likely resulting from damage of the respiratory chain Complex I and of the F₀F₁-ATP synthase.

Keywords: Liver preservation injury, Fatty liver, Mitochondria, Oxidative phosphorylation