Published online Oct 28, 2017. doi: 10.3748/wjg.v23.i40.7221
Peer-review started: August 19, 2017
First decision: August 29, 2017
Revised: September 10, 2017
Accepted: September 20, 2017
Article in press: September 19, 2017
Published online: October 28, 2017
Processing time: 71 Days and 14.7 Hours
To compare the effect of University of Wisconsin (UW) solution with or without metformin, an AMP-activated protein kinase (AMPK) activator, for preserving standard and marginal liver grafts of young and aged rats ex vivo by hypothermic machine perfusion (HMP).
Eighteen young (4 mo old) and 18 aged (17 mo old) healthy male SD rats were selected and randomly divided into three groups: control group, UW solution perfusion group (UWP), and UW solution with metformin perfusion group (MUWP). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-α) in the perfused liquid were tested. The expression levels of AMPK and endothelial nitric oxide synthase (eNOS) in liver sinusoidal endothelial cells were also examined. Additionally, microscopic evaluation of the harvested perfused liver tissue samples was done.
AST, ALT, LDH, IL-18 and TNF-α levels in the young and aged liver-perfused liquid were, respectively, significantly lower in the MUWP group than in the UWP group (P < 0.05), but no significant differences were found between the young and aged MUWP groups. Metformin increased the expression of AMPK and eNOS protein levels, and promoted the extracellular release of nitric oxide through activation of the AMPK-eNOS mediated pathway. Histological examination revealed that in the MUWP group, the extent of liver cells and tissue damage was significantly reduced compared with the UWP group.
The addition of metformin to the UW preservative solution for ex vivo HMP can reduce rat liver injury during cold ischemia, with significant protective effects on livers, especially of aged rats.
Core tip: Metformin can activate the AMP-activated protein kinase pathway that could enhance the activity of endothelial nitric oxide synthase and finally increase the generation of nitric oxide, which plays an important role in the protection of liver sinusoidal endothelial cells. Hence, our study was designed to evaluate the protective effect of University of Wisconsin storage solution with metformin for preserving standard and marginal liver grafts of young and aged rats ex vivo by hypothermic machine perfusion (HMP). According to the results, HMP with metformin plays a significant protective role for liver grafts during cold ischemia, with significant effects especially for aged-marginal donors.