Erythropoietin strongly protects the liver from ischemia-reperfusion injury in a pig model.

Abstract

BACKGROUND/AIMS: We investigated, for the first time, the protective effect of erythropoietin (EPO) against liver ischemia-reperfusion (I-R) injury in a pig model. METHODOLOGY: 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.