title: MitoQ blunts mitochondrial and renal damage during cold preservation of porcine kidneys.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Nirmala
authors.initials: N
authors.lastname: Parajuli
authors.forename: Lia H
authors.initials: LH
authors.lastname: Campbell
authors.forename: Akira
authors.initials: A
authors.lastname: Marine
authors.forename: Kelvin G M
authors.initials: KG
authors.lastname: Brockbank
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Macmillan-Crow
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D015925:Cryopreservation; D004579:Electron Transport / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology*; D015538:Nitrosation / Q000187:drug effects; D009926:Organ Preservation; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D051381:Rats; D034421:Sus scrofa; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D009943:Organophosphorus Compounds; D011506:Proteins; D014451:Ubiquinone; C429014:mitoquinone