Lower expression of Nrf2 mRNA in older donor livers: a possible contributor to increased ischemia-reperfusion injury?
BACKGROUND
The cellular mechanisms involved in mediating cytoprotection against ischemia-reperfusion (IR) injury are not well understood. In animal models, NF-E2-related factor-2 (Nrf2) protects against IR injury by transcriptional activation of phase II antioxidants. Here, we investigate how the expression of Nrf2 mRNA in human donor livers in the setting of liver transplantation (LT) correlates with the histological damage associated with IR injury and whether or not this influences the outcome of LT.


METHODS
Pairs of biopsies were acquired from 14 donor livers; the first biopsy of each pair was taken at the start of the retrieval operation, prior to the IR phase of LT and the second at the end of transplantation. RNA was extracted from snap frozen tissue and cDNA was prepared. Nrf2 mRNA expression was determined using real-time polymerase chain reaction (PCR). The modified Suzuki scoring system was used for histological grading of IR injury and relevant donor, recipient, and after LT clinical data were compiled.


RESULTS
Nrf2 expression was observed in all biopsies, both before and after IR. Some donor organs had greater expression of Nrf2 mRNA before IR injury, and these organs had lower Suzuki scores and better liver functions (ALT) after LT. Donors of livers with greater Nrf2 levels were significantly younger (40.5 yrs, range 28-53 yrs) than those with low Nrf2 levels (55.5 yrs, range 48-61 yrs), P<0.05.


CONCLUSIONS
Livers from older donors have lower levels of Nrf2 perhaps exposing these organs to more IR-related damage.
National Liver Unit, St Vincent's University Hospital, Dublin, Ireland.
Muhammad B
MB
Zaman
Martin O
MO
Leonard
Elizabeth J
EJ
Ryan
Niamh P
NP
Nolan
Emir
E
Hoti
Donal
D
Maguire
Hugh
H
Mulcahy
Oscar
O
Traynor
Cormac T
CT
Taylor
John E
JE
Hegarty
Justin G
JG
Geoghegan
Cliona
C
O'Farrelly
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002102:Cadaver; D002423:Cause of Death; D006801:Humans; D008099:Liver / Q000254:growth & development / Q000473:pathology / Q000502:physiology*; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D015427:Reperfusion Injury / Q000453:epidemiology*; D014019:Tissue Donors
D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D012333:RNA, Messenger