EPOR2/ßcR2-independendent effects of low-dose epoetin-α in porcine liver transplantation.
Biosci Rep
; 37(6)2017 Dec 22.
Article
in En
| MEDLINE
| ID: mdl-29127105
ABSTRACT
Ischemia-reperfusion injury (IRI) remains a key component of graft damage during transplantation. Erythropoietin (EPO) induces anti-inflammatory and anti-apoptotic effects via the EPOR2/ßcR2 complex, with a potential risk of thrombosis. Previous work indicates that EPO has EPOR2/ßcR2-independent protective effects via direct effects on the endothelium. As the EPOR2/ßcR2 receptor has a very low affinity for EPO, we aimed to test the hypothesis that EPO doses below the level that stimulate this receptor elicit cytoprotective effects via endothelial stimulation in a porcine liver transplantation model. Landrace pigs underwent allogenic liver transplantation (follow-up 6 h) with a portojugular shunt. Animals were divided into two groups donor and recipient treatment with low-dose EPO (65 IU/kg) or vehicle, administered 6 h before cold perfusion and 30 min after warm reperfusion. Fourteen of 17 animals (82.4%) fulfilled the inclusion criteria. No differences were noted in operative values between the groups including hemoglobin, cold or warm ischemic time. EPO-treated animals showed a significantly lower histopathology score, reduced apoptosis, oxidative stress, and most important a significant up-regulation of endothelial nitric oxide (NO) synthase (eNOS). Donor and recipient treatment with low-dose EPO reduces the hepatic IRI via EPOR2/ßcR2-independent cytoprotective mechanisms and represents a clinically applicable way to reduce IRI.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Erythropoietin
/
Epoetin Alfa
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Biosci Rep
Year:
2017
Document type:
Article
Affiliation country:
Germany