PMID- 23139796
OWN - NLM
STAT- MEDLINE
DCOM- 20130423
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 11
DP  - 2012
TI  - MitoQ blunts mitochondrial and renal damage during cold preservation of porcine 
      kidneys.
PG  - e48590
LID - 10.1371/journal.pone.0048590 [doi]
LID - e48590
AB  - Cold preservation has greatly facilitated the use of cadaveric kidneys for 
      transplantation but damage occurs during the preservation episode. It is well 
      established that oxidant production increases during cold renal preservation and 
      mitochondria are a key target for injury. Our laboratory has demonstrated that 
      cold storage of renal cells and rat kidneys leads to increased mitochondrial 
      superoxide levels and mitochondrial electron transport chain damage, and that 
      addition of Mitoquinone (MitoQ) to the preservation solutions blunted this 
      injury. In order to better translate animal studies, the inclusion of large 
      animal models is necessary to develop safe preclinical protocols. Therefore, we 
      tested the hypothesis that addition of MitoQ to cold storage solution preserves 
      mitochondrial function by decreasing oxidative stress, leading to less renal 
      tubular damage during cold preservation of porcine kidneys employing a standard 
      criteria donor model. Results showed that cold storage significantly induced 
      oxidative stress (nitrotyrosine), renal tubular damage, and cell death. Using 
      High Resolution Respirometry and fresh porcine kidney biopsies to assess 
      mitochondrial function we showed that MitoQ significantly improved complex II/III 
      respiration of the electron transport chain following 24 hours of cold storage. 
      In addition, MitoQ blunted oxidative stress, renal tubular damage, and cell death 
      after 48 hours. These results suggested that MitoQ decreased oxidative stress, 
      tubular damage and cell death by improving mitochondrial function during cold 
      storage. Therefore this compound should be considered as an integral part of 
      organ preservation solution prior to transplantation.
FAU - Parajuli, Nirmala
AU  - Parajuli N
AD  - Department of Pharmacology and Toxicology, University of Arkansas for Medical 
      Sciences, Little Rock, Arkansas, USA.
FAU - Campbell, Lia H
AU  - Campbell LH
FAU - Marine, Akira
AU  - Marine A
FAU - Brockbank, Kelvin G M
AU  - Brockbank KG
FAU - Macmillan-Crow, Lee Ann
AU  - Macmillan-Crow LA
LA  - eng
GR  - R43 DK089659/DK/NIDDK NIH HHS/United States
GR  - R43DK089659/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121106
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Organophosphorus Compounds)
RN  - 0 (Proteins)
RN  - 1339-63-5 (Ubiquinone)
RN  - 47BYS17IY0 (mitoquinone)
SB  - IM
MH  - Animals
MH  - Cell Death/drug effects
MH  - *Cryopreservation
MH  - Electron Transport/drug effects
MH  - In Situ Nick-End Labeling
MH  - Kidney Tubules/*drug effects/*pathology
MH  - Male
MH  - Mitochondria/*drug effects/*pathology
MH  - Nitrosation/drug effects
MH  - *Organ Preservation
MH  - Organophosphorus Compounds/*pharmacology
MH  - Oxidative Stress/drug effects
MH  - Proteins/metabolism
MH  - Rats
MH  - Sus scrofa
MH  - Ubiquinone/*analogs & derivatives/pharmacology
PMC - PMC3490900
COIS- Competing Interests: Dr. MacMillan-Crow has a Provisional U.S. Patent Application 
      #PCT/US2010/057246- Mito Q Organ cold storage composition and methods of use. PCT 
      filed 11/18/2012, WO 201/063130 A1 published 05/26/2011. Dr. Campbell is an 
      employee and Dr. Brockbank is both an employee and owner of Cell & Tissue 
      Systems, Inc. This does not alter the authors' adherence to all the PLOS ONE 
      policies on sharing data and materials.
EDAT- 2012/11/10 06:00
MHDA- 2013/04/24 06:00
PMCR- 2012/11/06
CRDT- 2012/11/10 06:00
PHST- 2012/07/26 00:00 [received]
PHST- 2012/09/28 00:00 [accepted]
PHST- 2012/11/10 06:00 [entrez]
PHST- 2012/11/10 06:00 [pubmed]
PHST- 2013/04/24 06:00 [medline]
PHST- 2012/11/06 00:00 [pmc-release]
AID - PONE-D-12-22336 [pii]
AID - 10.1371/journal.pone.0048590 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(11):e48590. doi: 10.1371/journal.pone.0048590. Epub 2012 Nov 6.