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Hypothermic machine perfusion with metformin-University of Wisconsin solution for ex vivo preservation of standard and marginal liver grafts in a rat model.
World J Gastroenterol. 2017 Oct 28; 23(40):7221-7231.WJ

Abstract

AIM

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).

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Authors+Show Affiliations

Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.Institute of Advanced Surgical Techniques and Engineering, Regenerative Medicine and Surgery Engineering Research Center of Shaanxi Province, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.Department of Hepatobiliary and Vascular Surgery, the 521 Hospital of Ordnance Industry, Xi'an 710065, Shaanxi Province, China.Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China. huliangshuo1983@hotmail.com.Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

29142469

Citation

Chai, Yi-Chao, et al. "Hypothermic Machine Perfusion With metformin-University of Wisconsin Solution for Ex Vivo Preservation of Standard and Marginal Liver Grafts in a Rat Model." World Journal of Gastroenterology, vol. 23, no. 40, 2017, pp. 7221-7231.
Chai YC, Dang GX, He HQ, et al. Hypothermic machine perfusion with metformin-University of Wisconsin solution for ex vivo preservation of standard and marginal liver grafts in a rat model. World J Gastroenterol. 2017;23(40):7221-7231.
Chai, Y. C., Dang, G. X., He, H. Q., Shi, J. H., Zhang, H. K., Zhang, R. T., Wang, B., Hu, L. S., & Lv, Y. (2017). Hypothermic machine perfusion with metformin-University of Wisconsin solution for ex vivo preservation of standard and marginal liver grafts in a rat model. World Journal of Gastroenterology, 23(40), 7221-7231. https://doi.org/10.3748/wjg.v23.i40.7221
Chai YC, et al. Hypothermic Machine Perfusion With metformin-University of Wisconsin Solution for Ex Vivo Preservation of Standard and Marginal Liver Grafts in a Rat Model. World J Gastroenterol. 2017 Oct 28;23(40):7221-7231. PubMed PMID: 29142469.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypothermic machine perfusion with metformin-University of Wisconsin solution for ex vivo preservation of standard and marginal liver grafts in a rat model. AU - Chai,Yi-Chao, AU - Dang,Guo-Xin, AU - He,Hai-Qi, AU - Shi,Jian-Hua, AU - Zhang,Hong-Ke, AU - Zhang,Rui-Tao, AU - Wang,Bo, AU - Hu,Liang-Shuo, AU - Lv,Yi, PY - 2017/08/18/received PY - 2017/09/10/revised PY - 2017/09/20/accepted PY - 2017/11/17/entrez PY - 2017/11/17/pubmed PY - 2018/7/7/medline KW - AMP-activated protein kinase KW - Cold ischemia injury KW - Hypothermic machine perfusion KW - Liver Grafts KW - Metformin SP - 7221 EP - 7231 JF - World journal of gastroenterology JO - World J Gastroenterol VL - 23 IS - 40 N2 - AIM: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/29142469/Hypothermic_machine_perfusion_with_metformin_University_of_Wisconsin_solution_for_ex_vivo_preservation_of_standard_and_marginal_liver_grafts_in_a_rat_model_ L2 - https://www.wjgnet.com/1007-9327/full/v23/i40/7221.htm DB - PRIME DP - Unbound Medicine ER -