Metformin preconditioning improves hepatobiliary function and reduces injury in a rat model of normothermic machine perfusion and orthotopic transplantationWesterkamp, A. C., Fujiyoshi, M., Ottens, P. J., Nijsten, M. W. N., Touw, D. J., de Meijer, V. E., Lisman, T., Leuvenink, H. G. D., Moshage, H., Berendsen, T. A. & Porte, R. J., 2-Mar-2020, In : Transplantation. 35 p.
Research output: Contribution to journal › Article › Academic › peer-review
- Microbes in Health and Disease (MHD)
- Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE)
- Pharmaceutical Analysis
- Groningen Research Institute for Asthma and COPD (GRIAC)
- Biopharmaceuticals, Discovery, Design and Delivery (BDDD)
- Pharmacokinetics, Toxicology and Targeting
- Groningen Institute for Organ Transplantation (GIOT)
- Center for Liver, Digestive and Metabolic Diseases (CLDM)
- Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)
BACKGROUND: Preconditioning of donor livers prior to organ retrieval may improve organ quality after transplantation. We investigated whether preconditioning with metformin reduces preservation injury and improves hepatobiliary function in rat donor livers during ex situ normothermic machine perfusion (NMP) and after orthotopic liver transplantation.
METHODS: Lewis rats were administered metformin via oral gavage, after which a donor hepatectomy was performed followed by a standardized cold storage period of 4 hours. Graft assessment was carried out using NMP via double perfusion of the hepatic artery and portal vein. In an additional experiment, rat donor livers preconditioned with metformin were stored on ice for 4 hours and transplanted to confirm postoperative liver function and survival. Data was analyzed and compared with sham-fed controls.
RESULTS: Graft assessment using NMP confirmed that preconditioning significantly improved ATP production, markers for hepatobiliary function (total bile production, biliary bilirubin and bicarbonate), and significantly lowered levels of lactate, glucose and apoptosis. After orthotopic liver transplantation, metformin preconditioning significantly reduced transaminase levels.
CONCLUSION: Preconditioning with metformin lowers hepatobiliary injury and improves hepatobiliary function in an in situ and ex situ model of rat donor liver transplantation.
|Number of pages||35|
|Publication status||E-pub ahead of print - 2-Mar-2020|