Metformin Preconditioning Improves Hepatobiliary Function and Reduces Injury in a Rat Model of Normothermic Machine Perfusion and Orthotopic Transplantation
Autor: | Robert J. Porte, Ton Lisman, Masato Fujiyoshi, Andrie C. Westerkamp, Henri G. D. Leuvenink, Han Moshage, Petra J. Ottens, Tim A Berendsen, Vincent E de Meijer, Maarten W. N. Nijsten, Daan J Touw |
---|---|
Přispěvatelé: | 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), Nanomedicine & Drug Targeting, Groningen Institute for Organ Transplantation (GIOT), Center for Liver, Digestive and Metabolic Diseases (CLDM), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Medicinal Chemistry and Bioanalysis (MCB) |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Male
medicine.medical_specialty Transplantation Conditioning Bilirubin medicine.medical_treatment Urology Cold storage 030230 surgery Liver transplantation BILE-DUCT INJURY MECHANISMS 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine LEFT-VENTRICULAR FUNCTION medicine Animals Lactic Acid Original Basic Science—Liver Biliary Tract Cholesterol 7-alpha-Hydroxylase ATP Binding Cassette Transporter Subfamily B Member 11 Transplantation Machine perfusion business.industry ACTIVATED PROTEIN-KINASE Organ Preservation LIVER-TRANSPLANTATION Metformin APOPTOSIS Liver Transplantation Rats Perfusion Bicarbonates chemistry MYOCARDIAL-INFARCTION Rats Inbred Lew Models Animal HEART 030211 gastroenterology & hepatology GRAFTS Liver function business FARNESOID-X-RECEPTOR medicine.drug |
Zdroj: | Transplantation Transplantation, 104(9), E271-E280. LIPPINCOTT WILLIAMS & WILKINS |
ISSN: | 1534-6080 0041-1337 |
Popis: | Background. Preconditioning of donor livers before 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 performed 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 were 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. Conclusions. Preconditioning with metformin lowers hepatobiliary injury and improves hepatobiliary function in an in situ and ex situ model of rat donor liver transplantation. |
Databáze: | OpenAIRE |
Externí odkaz: |