Erythropoietin strongly protects the liver from ischemia-reperfusion injury in a pig model.
OBJECTIVE
We investigated, for the first time, the protective effect of erythropoietin (EPO) against liver ischemia-reperfusion (I-R) injury in a pig model.


METHODS
Partial hepatic ischemia was maintained for 60 min in a pig. Pigs were allocated to 4 groups (n=5 each): (1) Control group with I-R injury (Vehicle); (2) EPO group with I-R injury, given three injections of EPO at 5000 IU/kg (EPO5000x3); (3) EPO group with I-R injury, given a single injection of EPO at 5000 IU/kg (EPO5000x1); and (4) EPO group with I-R injury, given three injections of EPO at 500 IU/kg (EPO500x3). Liver function tests (AST, ALT, LDH), and TUNEL assay were performed.


RESULTS
Three hours after I-R injury, AST levels in the Vehicle, EPO5000x3, EPO5000x1, and EPO500 x3 groups were 1494.2 +/- 711.3 U/L, 307.3 +/- 127.6 UL, 296.5 +/- 9.2 U/L, and 474.6 +/- 242.0 UL, respectively (one-factor ANOVA, p = 0.020). At 3h the ALT and LDH levels in the Vehicle group were significantly higher than those in the EPO5000x3 and EPO5000x1 groups. Apoptotic indices in the Vehicle, EPO500x3, EPO5000x1, and EPO500x3 groups 3 h after I-R injury were 2.40 +/- 0.93, 1.36 +/- 0.12, 1.11 +/- 0.17, and 1.51 +/- 0.33, respectively. The apoptotic indices of the EPO5000x1 and EPO500x3 groups were significantly lower than that of the Vehicle group.


CONCLUSIONS
EPO treatment significantly ameliorated liver I-R injury in this pig model. The protective effect was exerted by the inhibition of apoptosis. These results will open the door for the clinical application of EPO in liver surgery.
Shimoda
Mitsugi
M
Second Department of Surgery, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu Shimotsuga 880, Tochigi 321-0293, Japan.
Sawada
Tokihiko
T
Iwasaki
Yoshimi
Y
Mori
Shozo
S
Kijima
Hiroaki
H
Okada
Toshie
T
Kubota
Keiichi
K
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000098:blood supply*; D008111:Liver Function Tests; D011897:Random Allocation; D015427:Reperfusion Injury / Q000517:prevention & control; D013552:Swine
D004921:Erythropoietin