PMID- 21159749 OWN - NLM STAT- MEDLINE DCOM- 20110421 LR - 20211020 IS - 1521-0103 (Electronic) IS - 0022-3565 (Print) IS - 0022-3565 (Linking) VI - 336 IP - 3 DP - 2011 Mar TI - The mitochondria-targeted antioxidant mitoquinone protects against cold storage injury of renal tubular cells and rat kidneys. PG - 682-92 LID - 10.1124/jpet.110.176743 [doi] AB - The majority of kidneys used for transplantation are obtained from deceased donors. These kidneys must undergo cold preservation/storage before transplantation to preserve tissue quality and allow time for recipient selection and transport. However, cold storage (CS) can result in tissue injury, kidney discardment, or long-term renal dysfunction after transplantation. We have previously determined mitochondrial superoxide and other downstream oxidants to be important signaling molecules that contribute to CS plus rewarming (RW) injury of rat renal proximal tubular cells. Thus, this study's purpose was to determine whether adding mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to University of Wisconsin (UW) preservation solution could offer protection against CS injury. CS was initiated by placing renal cells or isolated rat kidneys in UW solution alone (4 h at 4 degrees C) or UW solution containing MitoQ or its control compound, decyltriphenylphosphonium bromide (DecylTPP) (1 muM in vitro; 100 muM ex vivo). Oxidant production, mitochondrial function, cell viability, and alterations in renal morphology were assessed after CS exposure. CS induced a 2- to 3-fold increase in mitochondrial superoxide generation and tyrosine nitration, partial inactivation of mitochondrial complexes, and a significant increase in cell death and/or renal damage. MitoQ treatment decreased oxidant production ~2-fold, completely prevented mitochondrial dysfunction, and significantly improved cell viability and/or renal morphology, whereas DecylTPP treatment did not offer any protection. These findings implicate that MitoQ could potentially be of therapeutic use for reducing organ preservation damage and kidney discardment and/or possibly improving renal function after transplantation. FAU - Mitchell, Tanecia AU - Mitchell T AD - Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR, USA. FAU - Rotaru, Dumitru AU - Rotaru D FAU - Saba, Hamida AU - Saba H FAU - Smith, Robin A J AU - Smith RA FAU - Murphy, Michael P AU - Murphy MP FAU - MacMillan-Crow, Lee Ann AU - MacMillan-Crow LA LA - eng GR - T32-DK061921/DK/NIDDK NIH HHS/United States GR - R01-DK078936-S1/DK/NIDDK NIH HHS/United States GR - MC_U105663142/MRC_/Medical Research Council/United Kingdom GR - T32 DK061921/DK/NIDDK NIH HHS/United States GR - R01 DK078936/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20101215 PL - United States TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - 0 (Antioxidants) RN - 0 (Organophosphorus Compounds) RN - 0 (Protective Agents) RN - 1339-63-5 (Ubiquinone) RN - 47BYS17IY0 (mitoquinone) SB - IM EIN - J Pharmacol Exp Ther. 2012 Aug;342(2):596 MH - Animals MH - Antioxidants/*pharmacology MH - Cell Death/drug effects/physiology MH - Cell Line MH - Cold Temperature/*adverse effects MH - Dose-Response Relationship, Drug MH - Kidney/drug effects/metabolism/pathology MH - Kidney Tubules, Proximal/*drug effects/metabolism/pathology MH - Male MH - Mitochondria/*drug effects/metabolism/pathology MH - Organ Preservation/*adverse effects MH - Organophosphorus Compounds/*pharmacology MH - Oxidative Stress/drug effects/physiology MH - Protective Agents/pharmacology MH - Rats MH - Rats, Inbred F344 MH - Ubiquinone/*pharmacology PMC - PMC3382740 EDAT- 2010/12/17 06:00 MHDA- 2011/04/22 06:00 PMCR- 2012/03/01 CRDT- 2010/12/17 06:00 PHST- 2010/12/17 06:00 [entrez] PHST- 2010/12/17 06:00 [pubmed] PHST- 2011/04/22 06:00 [medline] PHST- 2012/03/01 00:00 [pmc-release] AID - jpet.110.176743 [pii] AID - 3669879 [pii] AID - 10.1124/jpet.110.176743 [doi] PST - ppublish SO - J Pharmacol Exp Ther. 2011 Mar;336(3):682-92. doi: 10.1124/jpet.110.176743. Epub 2010 Dec 15.