MitoQ blunts mitochondrial and renal damage during cold preservation of porcine kidneys

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 demon...

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Veröffentlicht in:PloS one 2012-11, Vol.7 (11), p.e48590
Hauptverfasser: Parajuli, Nirmala, Campbell, Lia H, Marine, Akira, Brockbank, Kelvin G M, Macmillan-Crow, Lee Ann
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creator Parajuli, Nirmala
Campbell, Lia H
Marine, Akira
Brockbank, Kelvin G M
Macmillan-Crow, Lee Ann
description 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.
doi_str_mv 10.1371/journal.pone.0048590
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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. 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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. 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23139796</pmid><doi>10.1371/journal.pone.0048590</doi><tpages>e48590</tpages><oa>free_for_read</oa></addata></record>
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subjects Abdomen
Animal models
Animals
Antioxidants
Apoptosis
Biochemistry
Biology
Biosynthesis
Buffers
Cadavers
Cell death
Cell Death - drug effects
Cold storage
Coronary vessels
Cryopreservation
Cytochrome
Disease
Electron transport
Electron Transport - drug effects
Electron transport chain
Hogs
In Situ Nick-End Labeling
Ischemia
Kidney transplantation
Kidney Tubules - drug effects
Kidney Tubules - pathology
Kidneys
Laboratory animals
Male
Medicine
Mitochondria
Mitochondria - drug effects
Mitochondria - pathology
Mortality
Nitrosation - drug effects
Nitrotyrosine
Organ Preservation
Organophosphorus Compounds - pharmacology
Oxidative stress
Oxidative Stress - drug effects
Oxidizing agents
Pharmacology
Proteins - metabolism
Rats
Respirometry
Rodents
Storage
Superoxide
Superoxides
Sus scrofa
Toxicology
Transplantation
Transplants & implants
Ubiquinone - analogs & derivatives
Ubiquinone - pharmacology
title MitoQ blunts mitochondrial and renal damage during cold preservation of porcine kidneys
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