title: Cyclosporin-A does not prevent cold ischemia/reperfusion injury of rat livers.
abstract: Cyclosporin-A (CsA) has been reported to protect livers from warm ischemia/reperfusion (I/R) injury. To study if CsA has also a protective effect on cold I/R injury, two models were used: the isolated perfused rat liver (IPRL) and the orthotopic rat liver transplantation (ORLT). (1) IPRL: Livers were preserved for 24 h (5°C) in University of Wisconsin (UW) solution alone (group 1), with CsA (400 nM) dissolved in dimethylsulfoxide (50 μM) (group 2), and with dimethylsulfoxide (DMSO) alone (group 3). Livers were reperfused for 60 min (37°C) (n = 8/group). Cell necrosis was evaluated by trypan blue uptake and apoptosis by laddering and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and by caspase-3 activation. Marked and similar sinusoidal endothelial cell necrosis was found in the three groups while apoptosis was found similarly deceased in groups 2 and 3 compared with group 1. (2) ORLT: Donors received either CsA (5 mg/kg) or corn oil 24 h before transplantation. Recipients were sacrificed after 240 min; cell necrosis and apoptosis were then evaluated. No difference was found between treated and control groups. The current data strongly suggest that CsA has no protective effect on hepatic cold I/R injury. Hepatocyte apoptosis can be reduced by antioxidants, as occurred with DMSO, but introduction of CsA does not provide additional protective effect.
authors.affiliation: Centre de Recherche, Centre Hospitalier, Université de Montréal, Hôpital Saint Luc, Montréal, Québec, Canada.
authors.forename: Esther
authors.initials: E
authors.lastname: Tarrab
authors.forename: Pierre-Michel
authors.initials: PM
authors.lastname: Huet
authors.forename: Antoine
authors.initials: A
authors.lastname: Brault
authors.forename: Bernard
authors.initials: B
authors.lastname: Rocheleau
authors.forename: Marina
authors.initials: M
authors.lastname: Laurens
authors.forename: Dominique
authors.initials: D
authors.lastname: Crenesse
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D050377:Cold Ischemia; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004727:Endothelium / Q000187:drug effects / Q000473:pathology; D005978:Glutathione / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology*; D016031:Liver Transplantation / Q000473:pathology; D008297:Male; D023421:Models, Animal; D019188:Organ Preservation Solutions / Q000494:pharmacology; D011887:Raffinose / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology* / Q000517:prevention & control*
chemical_list: D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D016572:Cyclosporine; D053148:Caspase 3; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D004121:Dimethyl Sulfoxide