Protection by cyclosporin A of mitochondrial and cellular functions during a cold preservation-warm reperfusion of rat liver

European Journal of Pharmacology
Catherine PlinDidier Morin

Abstract

Liver transplantation is an effective therapeutic option for end-stage liver disease, but initial poor graft function still occurs, often related to cold preservation-warm reperfusion (CPWR) conditions. Damages to mitochondria could be implicated in hepatocyte cell death since opening of the permeability transition pore (PTP) can lead to necrosis and apoptosis. The purpose of this study was to test the hypothesis that inhibition of mitochondrial permeability transition by cyclosporin A could improve rat liver mitochondrial and hepatocellular parameters after 24-h cold preservation followed by a warm reperfusion in Krebs-Henseleit Buffer. Mitochondrial functions were assessed by measuring respiratory parameters, swelling, cytochrome c release and caspases activation. Hepatocyte injury was assessed by evaluation of ATP energetic charge, lactate dehydrogenase (LDH) leakage, apoptosis and necrosis. Results show that CPWR induces liver mitochondrial and cellular damages. CPWR induced damages on the mitochondrial respiratory chain, leading to mitochondrial swelling. The consequences are the loss of ATP energetic charge, the initiation of apoptosis through cytochrome c release and the activation of caspases. Cyclosporin A partially pr...Continue Reading

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Citations

Feb 13, 2007·Apoptosis : an International Journal on Programmed Cell Death·Andrea Rasola, Paolo Bernardi
Sep 19, 2012·Journal of Bioenergetics and Biomembranes·F A García-GilJ J García
Aug 12, 2006·Canadian Journal of Physiology and Pharmacology·Marjolaine DuvalPierre S Haddad
May 12, 2012·The Journal of Surgical Research·Georgios Tsoulfas
Jun 24, 2011·The Journal of Surgical Research·Esther TarrabDominique Crenesse
Jun 30, 2012·Biochemistry Research International·Davide Degli EspostiAntoinette Lemoine
Mar 20, 2013·Cell Transplantation·Hongling LiuScott L Nyberg
May 3, 2006·The FEBS Journal·Paolo BernardiMichael A Forte

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