Ischemic preconditioning improves liver regeneration by sustaining energy metabolism after partial hepatectomy under ischemia in rats.
BACKGROUND
The protective effect of ischemic preconditioning (IPC) has been reported on improvement of survival, reduction of liver necrosis and enhancement of the regenerative capacity of hepatocytes after partial hepatectomy. This study was undertaken to confirm that IPC has a significant impact on regeneration of hepatocytes after partial hepatectomy in ischemically damaged liver. In addition, we sought to examine the role of adenine nucleotides in this process.


METHODS
Wistar rats were subjected to 60 min of total hepatic ischemia, followed by 70% hepatectomy. The animals were subdivided into an IPC (10/15 min) group and a non-IPC (control) group. Liver function tests and arginase activity were analyzed. Hepatic adenosine triphosphate (ATP), adenosine diphosphate and adenosine monophosphate were measured using gradient high-performance liquid chromatography. The liver regeneration was identified using relative liver weight and proliferating cell nuclear antigen (PCNA) labeling index.


RESULTS
IPC treatment improved serum liver enzymes and tissue arginase activity (P<0.05) when compared with the control group. The preconditioned livers were associated with upregulation of ATP expression and also increased tissue energy charge. Regenerated liver weight in the IPC group was significantly higher than in the control group (P<0.05). The PCNA labeling index in the remnant livers in the IPC group was also significantly increased at 24 and 48 h after partial hepatectomy (P<0.05).


CONCLUSIONS
These results suggest that IPC-augmented liver regeneration after hepatectomy, probably due to the stabilization of energy metabolism in rats.
Kerem
Mustafa
M
Department of General Surgery, Faculty of Medicine, Gazi University, Ankara, Turkey. mkerem@gazi.edu.tr
Bedirli
Abdulkadir
A
Ofluoglu
Ebru
E
Deniz
Kemal
K
Turkozkan
Nurten
N
Pasaoglu
Hatice
H
Sakrak
Omer
O
D000255:Adenosine Triphosphate / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D006498:Hepatectomy; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000255:Adenosine Triphosphate; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase