The mitochondria-targeted antioxidant mitoquinone protects against cold storage injury of renal tubular cells and rat kidneys.

TitleThe mitochondria-targeted antioxidant mitoquinone protects against cold storage injury of renal tubular cells and rat kidneys.
Publication TypeJournal Article
Year of Publication2011
AuthorsMitchell, T, Rotaru, D, Saba, H, Smith, RAJ, Murphy, MP, MacMillan-Crow, LAnn
JournalJ Pharmacol Exp Ther
Volume336
Issue3
Pagination682-92
Date Published2011 Mar
ISSN1521-0103
KeywordsAnimals, Antioxidants, Cell Death, Cell Line, Cold Temperature, Dose-Response Relationship, Drug, Kidney, Kidney Tubules, Proximal, Male, Mitochondria, Organ Preservation, Organophosphorus Compounds, Oxidative Stress, Protective Agents, Rats, Rats, Inbred F344, Ubiquinone
Abstract

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°C) or UW solution containing MitoQ or its control compound, decyltriphenylphosphonium bromide (DecylTPP) (1 μM in vitro; 100 μM 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.

DOI10.1124/jpet.110.176743
Alternate JournalJ. Pharmacol. Exp. Ther.
Citation Key10.1124/jpet.110.176743
PubMed ID21159749
PubMed Central IDPMC3382740
Grant ListT32-DK061921 / DK / NIDDK NIH HHS / United States
R01-DK078936-S1 / DK / NIDDK NIH HHS / United States
MC_U105663142 / / Medical Research Council / United Kingdom
T32 DK061921 / DK / NIDDK NIH HHS / United States
R01 DK078936 / DK / NIDDK NIH HHS / United States