PMID- 33134502
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220418
IS  - 2373-8731 (Print)
IS  - 2373-8731 (Electronic)
IS  - 2373-8731 (Linking)
VI  - 6
IP  - 8
DP  - 2020 Aug
TI  - Significant Improvement in Rat Kidney Cold Storage Using UW Organ Preservation 
      Solution Supplemented With the Immediate-Acting PrC-210 Free Radical Scavenger.
PG  - e578
LID - 10.1097/TXD.0000000000001032 [doi]
LID - e578
AB  - Ischemia-reperfusion injury, including injury from warm- and cold-ischemia (CI) 
      organ storage, remains a significant problem for all solid organ transplants. 
      Suppressing CI damage would reduce delayed graft function and increase the donor 
      organ pool size. PrC-210 has demonstrated superior prevention of damage in 
      several preclinical studies as an immediate-acting free-radical scavenger. Here, 
      we describe its profound efficacy in suppressing CI injury in a rat kidney model. 
      METHODS: Kidneys in 300 gm Sprague-Dawley rats were perfused in situ with UW 
      solution with or without added PrC-210 and then stored at 4 degrees C in the same 
      solution for 0 to 48 hours. When procured, kidney-activated caspase-3 level (a 
      marker of cell death) was measured, and direct histological analysis of kidneys 
      was performed to assess PrC-210 protective efficacy. In vitro analyses of 
      PrC-210-conferred protection to isolated rat kidneys or naked DNA were also 
      performed. RESULTS: A single 15 seconds in situ perfusion of kidneys with 20 
      mmol/L PrC-210 in UW solution resulted in significant reductions in (1) 30-hour 
      CI-induced kidney-activated caspase level (P < 0.0001); activated caspase was 
      reduced to levels not significantly different than control activated caspase 
      levels seen in unperturbed kidneys, (2) 30-hour CI-induced renal Tubular Injury 
      Scores (P = 0.0004) where brush border and tubular necrosis were markedly 
      reduced, (3) PrC-210 conferred 100% protection against .OH damage to naked DNA 
      and isolated kidney mitochondria while current UW solution antioxidants were 
      without protective effect. CONCLUSIONS: A single PrC-210-UW solution perfusion of 
      rat kidneys upon removal from the rat profoundly reduced caspase and renal 
      tubular injury in kidneys exposed to 30 hours of CI organ storage. These findings 
      support further development of the PrC-210 molecule to suppress or to prevent 
      ischemia-reperfusion injury in organ transplant and other ischemia-reperfusion 
      injury settings.
CI  - Copyright (c) 2020 The Author(s). Transplantation Direct. Published by Wolters 
      Kluwer Health, Inc.
FAU - Verhoven, Bret M
AU  - Verhoven BM
AD  - Division of Organ Transplant, Department of Surgery, University of 
      Wisconsin-Madison, Madison, WI.
FAU - Karim, Aos S
AU  - Karim AS
AD  - Division of Organ Transplant, Department of Surgery, University of 
      Wisconsin-Madison, Madison, WI.
FAU - Bath, Natalie M
AU  - Bath NM
AD  - Division of Organ Transplant, Department of Surgery, University of 
      Wisconsin-Madison, Madison, WI.
FAU - Sarabia Fahl, Carol J
AU  - Sarabia Fahl CJ
AD  - Wisconsin Institutes for Medical Research, Department of Oncology, University of 
      Wisconsin-Madison, Madison, WI.
FAU - Wilson, Nancy A
AU  - Wilson NA
AD  - Division of Organ Transplant, Department of Surgery, University of 
      Wisconsin-Madison, Madison, WI.
FAU - Redfield, Robert R 3rd
AU  - Redfield RR 3rd
AD  - Division of Organ Transplant, Department of Surgery, University of 
      Wisconsin-Madison, Madison, WI.
FAU - Fahl, William E
AU  - Fahl WE
AD  - Wisconsin Institutes for Medical Research, Department of Oncology, University of 
      Wisconsin-Madison, Madison, WI.
LA  - eng
GR  - KL2 TR002374/TR/NCATS NIH HHS/United States
GR  - R03 CA176799/CA/NCI NIH HHS/United States
GR  - T32 AI125231/AI/NIAID NIH HHS/United States
GR  - UL1 TR002373/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20200715
PL  - United States
TA  - Transplant Direct
JT  - Transplantation direct
JID - 101651609
PMC - PMC7581037
COIS- The authors declare no conflicts of interest.
EDAT- 2020/11/03 06:00
MHDA- 2020/11/03 06:01
PMCR- 2020/07/15
CRDT- 2020/11/02 06:21
PHST- 2020/04/09 00:00 [received]
PHST- 2020/06/03 00:00 [revised]
PHST- 2020/06/06 00:00 [accepted]
PHST- 2020/11/02 06:21 [entrez]
PHST- 2020/11/03 06:00 [pubmed]
PHST- 2020/11/03 06:01 [medline]
PHST- 2020/07/15 00:00 [pmc-release]
AID - 10.1097/TXD.0000000000001032 [doi]
PST - epublish
SO  - Transplant Direct. 2020 Jul 15;6(8):e578. doi: 10.1097/TXD.0000000000001032. 
      eCollection 2020 Aug.