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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-44084

Pappo, O; Ben-Ari, Z; Shevtsov, E; Avlas, O; Gassmann, M; Ravid, A; Cheporko, Y; Hochhauser, E (2010). The role of excessive versus acute administration of erythropoietin in attenuating hepatic ischemia-reperfusion injury. Canadian Journal of Physiology and Pharmacology, 88(12):1130-1137.

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Abstract

Ischemia-reperfusion injury (I/R) is the main cause of primary graft nonfunction. Our aim was to evaluate the effect of excessive versus acute administration of erythropoietin (EPO) in attenuating the hepatic injury induced by I/R in mice. The effect of segmental (70%) hepatic ischemia was evaluated in a transgenic mouse line with constitutive overexpression of human EPO cDNA and in wild-type (WT) mice. Mice were randomly allocated to 5 main experimental groups: (i) WT-sham, (ii) WT ischemia, (iii) WT ischemia + recombinant human erythropoietin (rhEPO), (iv) transgenic-sham, and (v) transgenic ischemia. The EPO-pretreated mice showed a significant reduction in liver enzyme levels and intrahepatic caspase-3 activity and fewer apoptotic hepatocytes (p < 0.05 for all) compared with the WT untreated I/R group. EPO decreased c-Jun N-terminal kinase (JNK) phosphorylation and nuclear factor-κB (NF-κB) expression during I/R. In transgenic I/R livers, baseline histology showed diffused hepatic injury, and no significant beneficial effect was noted between the WT untreated and the transgenic I/R mice. In conclusion, acute pretreatment with EPO in WT mice attenuated in vivo I/R liver injury. However, in excessive EPO overexpression, the initial liver injury abolished the beneficial effect of EPO. These findings have important implications for the potential use of acute EPO in I/R injury during liver transplantation.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
DDC:570 Life sciences; biology
610 Medicine & health
Date:2010
Deposited On:01 Feb 2011 15:24
Last Modified:27 Nov 2013 17:24
Publisher:National Research Council Canada
ISSN:0008-4212
Publisher DOI:10.1139/y10-091
PubMed ID:21164559
Citations:Web of Science®. Times Cited: 5
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Scopus®. Citation Count: 7

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