The Mitochondria-Targeted Antioxidant Mitoquinone Protects against Cold Storage Injury of Renal Tubular Cells and Rat Kidneys
| Autor: | Michael P. Murphy, Robin A.J. Smith, Dumitru Rotaru, Tanecia Mitchell, Lee Ann MacMillan-Crow, Hamida Saba |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Ubiquinone Cold storage Pharmacology Biology Mitochondrion Kidney Protective Agents Antioxidants Cell Line Kidney Tubules Proximal chemistry.chemical_compound Organophosphorus Compounds medicine Animals Viaspan Viability assay MitoQ Cell Death Dose-Response Relationship Drug Kidney metabolism Organ Preservation Rats Inbred F344 Mitochondria Rats Surgery Cold Temperature Transplantation Oxidative Stress medicine.anatomical_structure chemistry Molecular Medicine Gastrointestinal Hepatic Pulmonary and Renal |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 336:682-692 |
| ISSN: | 1521-0103 0022-3565 |
| DOI: | 10.1124/jpet.110.176743 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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