Improvement of steatotic rat liver function with a defatting cocktail during ex situ normothermic machine perfusion is not directly related to liver fat content.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
24
09
2019
accepted:
23
04
2020
entrez:
13
5
2020
pubmed:
13
5
2020
medline:
31
7
2020
Statut:
epublish
Résumé
There is a significant organ shortage in the field of liver transplantation, partly due to a high discard rate of steatotic livers from donors. These organs are known to function poorly if transplanted but make up a significant portion of the available pool of donated livers. This study demonstrates the ability to improve the function of steatotic rat livers using a combination of ex situ machine perfusion and a "defatting" drug cocktail. After 6 hours of perfusion, defatted livers demonstrated lower perfusate lactate levels and improved bile quality as demonstrated by higher bile bicarbonate and lower bile lactate. Furthermore, defatting was associated with decreased gene expression of pro-inflammatory cytokines and increased expression of enzymes involved in mitochondrial fatty acid oxidation. Rehabilitation of marginal or discarded steatotic livers using machine perfusion and tailored drug therapy can significantly increase the supply of donor livers for transplantation.
Identifiants
pubmed: 32396553
doi: 10.1371/journal.pone.0232886
pii: PONE-D-19-26883
pmc: PMC7217452
doi:
Substances chimiques
Bicarbonates
0
Cytokines
0
Lactic Acid
33X04XA5AT
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0232886Subventions
Organisme : NIBIB NIH HHS
ID : R21 EB020819
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK114506
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK084053
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107875
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK096075
Pays : United States
Déclaration de conflit d'intérêts
Dr. Uygun is inventor on pending patents relevant to this study (WO/2011/002926; WO/2011/35223) and has a provisional patent application relevant to this study (MGH 22743). Dr. Uygun has a financial interest in Organ Solutions, a company focused on developing organ preservation technology. Dr. Uygun’s interests are managed by the MGH and Partners HealthCare in accordance with their conflict of interest policies. This does not alter our adherence to PLOS ONE policies on sharing data and materials”.
Références
Hepatology. 2013 Dec;58(6):1941-52
pubmed: 23703580
Transplantation. 2011 Aug 15;92(3):289-95
pubmed: 21681143
Curr Opin Lipidol. 2013 Apr;24(2):171-7
pubmed: 23481229
Semin Liver Dis. 2001;21(1):105-13
pubmed: 11296690
Hepatology. 2019 Jul;70(1):431-433
pubmed: 30681724
Liver Transpl. 2014 Aug;20(8):1000-11
pubmed: 24802973
Methods Mol Biol. 2017;1558:235-253
pubmed: 28150241
Science. 2005 Jan 21;307(5708):426-30
pubmed: 15604363
Gastroenterology. 2016 May;150(5):1147-1159.e5
pubmed: 26874076
Am J Physiol Gastrointest Liver Physiol. 2007 May;292(5):G1385-95
pubmed: 17307725
Anat Rec (Hoboken). 2008 Jun;291(6):684-92
pubmed: 18484615
Curr Pharm Des. 2010 Jun;16(17):1913-20
pubmed: 20370672
Am J Gastroenterol. 2003 Feb;98(2):466-70
pubmed: 12591070
J Gastroenterol. 2018 Mar;53(3):362-376
pubmed: 29247356
Liver Int. 2014 Oct;34(9):1414-27
pubmed: 24905412
HPB Surg. 2018 Nov 1;2018:6094936
pubmed: 30515073
Horm Metab Res. 2019 Sep;51(9):602-607
pubmed: 31132798
PLoS One. 2018 Jul 25;13(7):e0201419
pubmed: 30044872
Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7500-2
pubmed: 10852961
Br J Pharmacol. 2016 Nov;173(22):3248-3260
pubmed: 27590029
Liver Transpl. 2019 Jul;25(7):991-992
pubmed: 31077626
Br J Surg. 2007 Aug;94(8):1002-8
pubmed: 17497653
J Gastrointest Surg. 2015 Sep;19(9):1713-24
pubmed: 25917535
Transplantation. 2005 Sep 15;80(5):608-12
pubmed: 16177634
Mol Metab. 2017 Jan 06;6(3):256-266
pubmed: 28271032
HPB Surg. 2018 Apr 23;2018:6867986
pubmed: 29849531
JAMA. 1999 Nov 3;282(17):1659-64
pubmed: 10553793
Genome Res. 2003 Nov;13(11):2498-504
pubmed: 14597658
Liver Transpl. 2018 Feb;24(2):233-245
pubmed: 29125712
N Engl J Med. 2010 May 6;362(18):1675-85
pubmed: 20427778
Transplantation. 2017 Jul;101(7):1637-1644
pubmed: 28230641
Am J Transplant. 2018 Oct;18(10):2384-2399
pubmed: 29947472
Methods Mol Biol. 2017;1641:281-296
pubmed: 28748470
J Clin Epidemiol. 2001 Apr;54(4):343-9
pubmed: 11297884
Metab Eng. 2009 Jul-Sep;11(4-5):274-83
pubmed: 19508897
Nature. 2018 May;557(7703):50-56
pubmed: 29670285
Liver Transpl. 2019 Jul;25(7):1007-1022
pubmed: 30821045
Lancet. 2015 Mar 14;385(9972):956-65
pubmed: 25468160
J Physiol Biochem. 2011 Dec;67(4):569-76
pubmed: 21656273
Pharmacol Ther. 2017 Nov;179:142-157
pubmed: 28546081