PMID- 21696775 OWN - NLM STAT- MEDLINE DCOM- 20120713 LR - 20131121 IS - 1095-8673 (Electronic) IS - 0022-4804 (Linking) VI - 175 IP - 2 DP - 2012 Jun 15 TI - Cyclosporin-A does not prevent cold ischemia/reperfusion injury of rat livers. PG - 333-42 LID - 10.1016/j.jss.2011.04.018 [doi] AB - 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 degrees C) in University of Wisconsin (UW) solution alone (group 1), with CsA (400 nM) dissolved in dimethylsulfoxide (50 muM) (group 2), and with dimethylsulfoxide (DMSO) alone (group 3). Livers were reperfused for 60 min (37 degrees 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. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Tarrab, Esther AU - Tarrab E AD - Centre de Recherche, Centre Hospitalier, Universite de Montreal, Hopital Saint Luc, Montreal, Quebec, Canada. FAU - Huet, Pierre-Michel AU - Huet PM FAU - Brault, Antoine AU - Brault A FAU - Rocheleau, Bernard AU - Rocheleau B FAU - Laurens, Marina AU - Laurens M FAU - Crenesse, Dominique AU - Crenesse D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110505 PL - United States TA - J Surg Res JT - The Journal of surgical research JID - 0376340 RN - 0 (Insulin) RN - 0 (Organ Preservation Solutions) RN - 0 (University of Wisconsin-lactobionate solution) RN - 63CZ7GJN5I (Allopurinol) RN - 83HN0GTJ6D (Cyclosporine) RN - EC 3.4.22.- (Caspase 3) RN - GAN16C9B8O (Glutathione) RN - K72T3FS567 (Adenosine) RN - N5O3QU595M (Raffinose) RN - YOW8V9698H (Dimethyl Sulfoxide) SB - IM CIN - J Surg Res. 2012 Jul;176(1):e1-3. PMID: 22575360 MH - Adenosine/pharmacology MH - Allopurinol/pharmacology MH - Animals MH - Apoptosis/drug effects MH - Caspase 3/metabolism MH - *Cold Ischemia MH - Cyclosporine/pharmacology/*therapeutic use MH - Dimethyl Sulfoxide/pharmacology MH - Endothelium/drug effects/pathology MH - Glutathione/pharmacology MH - Hepatocytes/drug effects/pathology MH - Insulin/pharmacology MH - Liver/*blood supply/enzymology/*pathology MH - Liver Transplantation/pathology MH - Male MH - Models, Animal MH - Organ Preservation Solutions/pharmacology MH - Raffinose/pharmacology MH - Rats MH - Rats, Inbred Lew MH - Regional Blood Flow/physiology MH - Reperfusion Injury/enzymology/*pathology/*prevention & control EDAT- 2011/06/24 06:00 MHDA- 2012/07/14 06:00 CRDT- 2011/06/24 06:00 PHST- 2011/01/18 00:00 [received] PHST- 2011/03/28 00:00 [revised] PHST- 2011/04/07 00:00 [accepted] PHST- 2011/06/24 06:00 [entrez] PHST- 2011/06/24 06:00 [pubmed] PHST- 2012/07/14 06:00 [medline] AID - S0022-4804(11)00369-6 [pii] AID - 10.1016/j.jss.2011.04.018 [doi] PST - ppublish SO - J Surg Res. 2012 Jun 15;175(2):333-42. doi: 10.1016/j.jss.2011.04.018. Epub 2011 May 5.