PMID- 30691853
OWN - NLM
STAT- MEDLINE
DCOM- 20191118
LR  - 20191118
IS  - 1095-8673 (Electronic)
IS  - 0022-4804 (Linking)
VI  - 235
DP  - 2019 Mar
TI  - Effects of Hepatic Ischemia-Reperfusion Injuries and NRF2 on Transcriptional 
      Activities of Bile Transporters in Rats.
PG  - 73-82
LID - S0022-4804(18)30693-0 [pii]
LID - 10.1016/j.jss.2018.09.057 [doi]
AB  - BACKGROUND: The effect of hepatic ischemia-reperfusion injury (IRI) on bile 
      transporter (BT) gene expression is unknown. We hypothesized that abnormal 
      expression of BTs during hepatic IRI is dependent on nuclear factor erythroid 
      2-related factor 2 (NRF2), which contributes to the cholestasis after 
      reperfusion. METHODS: Sham surgery and short (60 min) or long (90 min) periods of 
      warm ischemia time (WIT) with or without reperfusion for 24 h were applied to 
      wild-type Sprague-Dawley rats and Nrf2 knockout rats (n = 5 per group). At each 
      stage of IRI, the serum levels of aminotransferase, total bilirubin, and bile 
      acids were measured. In addition, hepatic tissue was sampled to determine the 
      histologic score of IRI (Suzuki score), measure adenosine triphosphate (ATP), and 
      identify the quantitative real-time polymerase chain reactions of BTs (Oatp1, 
      Ntcp, Mrp2, Bsep, and Mrp3). RESULTS: In short periods of WIT, BT expression 
      increased during the ischemia stage and returned to the baseline after 
      reperfusion. However, in long periods of WIT, BT expression did not increase 
      after ischemia and decreased further after reperfusion. Short WIT did not 
      increase BT expression in Nrf2 knockout animals. The level of BT expression was 
      correlated with the Suzuki score, the serum levels of aminotransferase, 
      bilirubin, and bile acids, and tissue ATP level. Stepwise multiple regression 
      analysis derived equations to predict the Suzuki score (R(2) = 76.8, P < 0.001), 
      serum total bilirubin (R(2) = 61.2, P < 0.001), and tissue ATP (R(2) = 61.1, 
      P < 0.001). CONCLUSIONS: Short WIT induces the transcriptional activities of BT, 
      whereas long WIT depresses them, and the effect was blunted by Nrf2 knockout 
      status. BT expression can be considered a surrogate marker for hepatic IRI.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Kim, Joohyun
AU  - Kim J
AD  - Division of Transplant Surgery, Department of Surgery, Medical College of 
      Wisconsin, Milwaukee, Wisconsin.
FAU - Martin, Alicia
AU  - Martin A
AD  - Division of Transplant Surgery, Department of Surgery, Medical College of 
      Wisconsin, Milwaukee, Wisconsin.
FAU - Yee, Jennifer
AU  - Yee J
AD  - Division of Transplant Surgery, Department of Surgery, Medical College of 
      Wisconsin, Milwaukee, Wisconsin.
FAU - Fojut, Lynn
AU  - Fojut L
AD  - Division of Transplant Surgery, Department of Surgery, Medical College of 
      Wisconsin, Milwaukee, Wisconsin.
FAU - Geurts, Aron M
AU  - Geurts AM
AD  - Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.
FAU - Oshima, Kiyoko
AU  - Oshima K
AD  - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, 
      Maryland.
FAU - Zimmerman, Michael A
AU  - Zimmerman MA
AD  - Division of Transplant Surgery, Department of Surgery, Medical College of 
      Wisconsin, Milwaukee, Wisconsin.
FAU - Hong, Johnny C
AU  - Hong JC
AD  - Division of Transplant Surgery, Department of Surgery, Medical College of 
      Wisconsin, Milwaukee, Wisconsin. Electronic address: jhong@mcw.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181024
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, rat)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Bile/*metabolism
MH  - Liver/*blood supply
MH  - Male
MH  - Membrane Transport Proteins/*genetics
MH  - NF-E2-Related Factor 2/*physiology
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/*metabolism
MH  - Transcription, Genetic
MH  - Warm Ischemia
OTO - NOTNLM
OT  - BSEP
OT  - Bile transporters
OT  - Hepatic injury marker
OT  - Ischemia-reperfusion injury
OT  - MRP2
OT  - MRP3
OT  - NRF2
OT  - NTCP
OT  - OATP1
OT  - Transcriptional activity
EDAT- 2019/01/30 06:00
MHDA- 2019/11/19 06:00
CRDT- 2019/01/30 06:00
PHST- 2018/04/18 00:00 [received]
PHST- 2018/09/07 00:00 [revised]
PHST- 2018/09/19 00:00 [accepted]
PHST- 2019/01/30 06:00 [entrez]
PHST- 2019/01/30 06:00 [pubmed]
PHST- 2019/11/19 06:00 [medline]
AID - S0022-4804(18)30693-0 [pii]
AID - 10.1016/j.jss.2018.09.057 [doi]
PST - ppublish
SO  - J Surg Res. 2019 Mar;235:73-82. doi: 10.1016/j.jss.2018.09.057. Epub 2018 Oct 24.