PMID- 34379880
OWN - NLM
STAT- MEDLINE
DCOM- 20220131
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Linking)
VI  - 22
IP  - 1
DP  - 2022 Jan
TI  - NRF2 assessment in discarded liver allografts: A role in allograft function and 
      salvage.
PG  - 58-70
LID - 10.1111/ajt.16789 [doi]
AB  - Antioxidant defence mechanisms, such as the nuclear factor-erythroid 
      2-related-factor-2 (NRF2) axis, are integral to oxidative stress responses and 
      ischemic injury. Hepatic antioxidant capacity is contingent on parenchymal 
      quality, and there is a need to develop new insights into key molecular 
      mechanisms in marginal liver allografts that might provide therapeutic targets. 
      This study examines the clinical relevance of NRF2 in donor livers and its 
      response to normothermic machine perfusion (NMP). Discarded donor livers (n = 40) 
      were stratified into a high NRF2 and low NRF2 group by quantifying NRF2 
      expression. High NRF2 livers had significantly lower transaminase levels, hepatic 
      vascular inflammation and peri-portal CD3(+) T cell infiltration. Human liver 
      allografts (n = 8) were then exposed to 6-h of NMP and high NRF2 livers had 
      significantly reduced liver enzyme alterations and improved lactate clearance. To 
      investigate these findings further, we used a rat fatty-liver model, treating 
      livers with an NRF2 agonist during NMP. Treated livers had increased NRF2 
      expression and reduced transaminase derangements following NMP compared to 
      vehicle control. These results support the association of elevated NRF2 
      expression with improved liver function. Targeting this axis could have a 
      rationale in future studies and NRF2 agonists may represent a supplemental 
      treatment strategy for rescuing marginal donor livers.
CI  - (c) 2021 The American Society of Transplantation and the American Society of 
      Transplant Surgeons.
FAU - Ahmed, Ola
AU  - Ahmed O
AUID- ORCID: 0000-0002-8778-6979
AD  - Department of Surgery, Section of Abdominal Transplantation, Washington 
      University School of Medicine, St. Louis, Missouri, USA.
AD  - School of Medicine, Trinity College Dublin, Dublin 2, Ireland.
FAU - Xu, Min
AU  - Xu M
AUID- ORCID: 0000-0002-0934-1237
AD  - Department of Surgery, Section of Abdominal Transplantation, Washington 
      University School of Medicine, St. Louis, Missouri, USA.
FAU - Zhou, Fangyu
AU  - Zhou F
AD  - Department of Surgery, Section of Abdominal Transplantation, Washington 
      University School of Medicine, St. Louis, Missouri, USA.
FAU - Wein, Alexander N
AU  - Wein AN
AUID- ORCID: 0000-0002-8813-3523
AD  - Department of Pathology and Immunology, Washington University School of Medicine, 
      St. Louis, Missouri, USA.
FAU - Upadhya, Gundumi A
AU  - Upadhya GA
AD  - Department of Surgery, Section of Abdominal Transplantation, Washington 
      University School of Medicine, St. Louis, Missouri, USA.
FAU - Ye, Li
AU  - Ye L
AD  - Department of Surgery, Section of Abdominal Transplantation, Washington 
      University School of Medicine, St. Louis, Missouri, USA.
FAU - Wong, Brian W
AU  - Wong BW
AUID- ORCID: 0000-0001-8447-3064
AD  - Department of Surgery, Section of Abdominal Transplantation, Washington 
      University School of Medicine, St. Louis, Missouri, USA.
FAU - Lin, Yiing
AU  - Lin Y
AD  - Department of Surgery, Section of Abdominal Transplantation, Washington 
      University School of Medicine, St. Louis, Missouri, USA.
FAU - O'Farrelly, Cliona
AU  - O'Farrelly C
AD  - School of Medicine, Trinity College Dublin, Dublin 2, Ireland.
AD  - School of Biochemistry & Immunology, Trinity College Dublin, Dublin 2, Ireland.
FAU - Chapman, William C
AU  - Chapman WC
AUID- ORCID: 0000-0002-0072-3239
AD  - Department of Surgery, Section of Abdominal Transplantation, Washington 
      University School of Medicine, St. Louis, Missouri, USA.
LA  - eng
PT  - Journal Article
DEP - 20210826
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Allografts
MH  - Animals
MH  - Liver
MH  - *Liver Transplantation
MH  - NF-E2-Related Factor 2
MH  - Organ Preservation
MH  - Perfusion
MH  - Rats
MH  - *Reperfusion Injury
OTO - NOTNLM
OT  - basic (laboratory) research/science
OT  - biomarker
OT  - cellular biology
OT  - immune regulation
OT  - ischemia reperfusion injury (IRI)
OT  - liver allograft function/dysfunction
OT  - liver transplantation/hepatology
OT  - organ perfusion and preservation
EDAT- 2021/08/12 06:00
MHDA- 2022/02/01 06:00
CRDT- 2021/08/11 17:32
PHST- 2021/06/23 00:00 [revised]
PHST- 2021/04/23 00:00 [received]
PHST- 2021/07/19 00:00 [accepted]
PHST- 2021/08/12 06:00 [pubmed]
PHST- 2022/02/01 06:00 [medline]
PHST- 2021/08/11 17:32 [entrez]
AID - S1600-6135(22)08042-X [pii]
AID - 10.1111/ajt.16789 [doi]
PST - ppublish
SO  - Am J Transplant. 2022 Jan;22(1):58-70. doi: 10.1111/ajt.16789. Epub 2021 Aug 26.