Erythropoietin reduces ischemia-reperfusion injury in the rat liver.
BACKGROUND
Human recombinant erythropoietin (Epo) has recently been shown to be a potent protector of ischemic damage in various organ systems. A significant reduction of stroke injury following cerebral ischemia has been postulated as well as improved cardiomyocyte function after myocardial infarction in tissue pretreated with Epo. It was the aim of this study to evaluate the effects of Epo in liver ischemia.


METHODS
Rats were subjected to 45 min of warm hepatic ischemia. Animals were either pretreated with 1,000 IU of Epo in three doses or received 1,000 IU into the portal vein 30 min before ischemia. Control animals received saline at the same time points before ischemia. Animals were than sacrificed 6, 12, 24, 48 h and 7 days after surgery and transaminases were measured. Liver specimens were evaluated regarding apoptosis, necrosis and regeneration capacity.


RESULTS
Apoptosis rates were dramatically reduced in animals pretreated with Epo while mRNA of tumor necrosis factor-alpha and STAT-3 were upregulated in all groups. Intraportal venous injection displayed superiority to subcutaneous preconditioning. Transaminases were significantly reduced among the Epo-treated animals after 6 and 12 h.


CONCLUSIONS
Our data suggests a protective effect of Epo in warm hepatic ischemia and reperfusion injury in the rat.
Schmeding
M
M
Department of General and Transplantation Surgery, Charité University Medical Center Berlin, Campus Virchow Clinic, Berlin, Germany. maximilian.schmeding@charite.de
Neumann
U P
UP
Boas-Knoop
S
S
Spinelli
A
A
Neuhaus
P
P
D000818:Animals; D004921:Erythropoietin / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin