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.
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Authors | Esther Tarrab, Pierre-Michel Huet, Antoine Brault, Bernard Rocheleau, Marina Laurens, Dominique Crenesse |
Journal | The Journal of surgical research
(J Surg Res)
Vol. 175
Issue 2
Pg. 333-42
(Jun 15 2012)
ISSN: 1095-8673 [Electronic] United States |
PMID | 21696775
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Chemical References |
- Insulin
- Organ Preservation Solutions
- University of Wisconsin-lactobionate solution
- Allopurinol
- Cyclosporine
- Caspase 3
- Glutathione
- Adenosine
- Raffinose
- Dimethyl Sulfoxide
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Topics |
- Adenosine
(pharmacology)
- Allopurinol
(pharmacology)
- Animals
- Apoptosis
(drug effects)
- Caspase 3
(metabolism)
- Cold Ischemia
- Cyclosporine
(pharmacology, therapeutic use)
- Dimethyl Sulfoxide
(pharmacology)
- Endothelium
(drug effects, pathology)
- Glutathione
(pharmacology)
- Hepatocytes
(drug effects, pathology)
- Insulin
(pharmacology)
- Liver
(blood supply, enzymology, pathology)
- Liver Transplantation
(pathology)
- Male
- Models, Animal
- Organ Preservation Solutions
(pharmacology)
- Raffinose
(pharmacology)
- Rats
- Rats, Inbred Lew
- Regional Blood Flow
(physiology)
- Reperfusion Injury
(enzymology, pathology, prevention & control)
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