THE DUAL EFFECT OF ERYTHROPOIETIN IN LIVER
PROTECTION AND REGENERATION FOLLOWING
SUBTOTAL HEPATECTOMY IN RATS
Ben-Ari Z 1. , Taya R2. , Pappo O 3 ., Cheporko Y4.,Kurswald E 4.
, Ravid A 5. , Graif F 2 ., Hochhauser E4.
1
Liver Institute , 2 Department of Surgery A, 3Department of
Histopathology, Beilinson Hospital, 4Liver Transplantation
Laboratory, 5Laboratory of Endocrine Immunology, Felsenstein
Medical Research Center, Petah Tiqwa, and Sackler School of
Medicine, Tel Aviv University, Israel
Background: Resection of hepatic tumors offers the only
curative option for primary or secondary liver tumors. Excessive
resection leads to liver failure and death. Objective: to
investigate the role of rhEPO in liver protection and regeneration
following subtotal hepatectomy. Methods: Rats undergoing 70%
hepatectomy received an intraperitoneal injection of rhEPO prior
to resection. Control animals were administered saline. Serum
liver enzyme, INR levels and intrahepatic caspase-3 activity
were measured. Apoptotic cells were identified by morphological
criteria, TUNEL assay, and immunohistochemistry for caspase-
3. Regeneration capacity of remnant livers was studied by
histology, immunohistochemistry for Ki-67, von Willebrand factor
(vWF) and ERK and NFκB signaling pathways. Results: Two
and 4 days following subtotal hepatectomy, the regenerated
liver/body weight (kg) ratio was statistically significant higher in
animals treated with rhEPO (p<0.005) compared with the control
group. Serum liver enzymes and INR levels in days 2 and 4
posthepatectomy were statistically significant lower in animals
pretreated with rhEPO (p<0.005) compared with the control
group. No statistically significant difference was noted in
intrahepatic hepatic caspase-3 activity, immunohistochemistry
for caspase-3 and the TUNEL assay between the control and
rhEPO pretreated group. At day 2 posthepatectomy the mitotic
figures, Ki-67, vWF expressions and ERK activity were
significantly higher in the rhEPO pretreated group (p<0.05)
compared with the control group. NFκB activity was higher in
both groups. Conclusions: rhEPO treatment may offer a
beneficial unique dual-function strategy for hepatic protection
and regeneration in the immediate post subtotal hepatectomy
period in rats.