title: The mitochondria-targeted antioxidant mitoquinone protects against cold storage injury of renal tubular cells and rat kidneys.
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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Tanecia
authors.initials: T
authors.lastname: Mitchell
authors.forename: Dumitru
authors.initials: D
authors.lastname: Rotaru
authors.forename: Hamida
authors.initials: H
authors.lastname: Saba
authors.forename: Robin A J
authors.initials: RA
authors.lastname: Smith
authors.forename: Michael P
authors.initials: MP
authors.lastname: Murphy
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: MacMillan-Crow
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D003080:Cold Temperature / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009926:Organ Preservation / Q000009:adverse effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D014451:Ubiquinone / Q000494:pharmacology* / Q000031:analogs & derivatives
chemical_list: D000975:Antioxidants; D009943:Organophosphorus Compounds; D020011:Protective Agents; D014451:Ubiquinone; C429014:mitoquinone