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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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. |
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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. 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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0048590</identifier><identifier>PMID: 23139796</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>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</subject><ispartof>PloS one, 2012-11, Vol.7 (11), p.e48590</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Parajuli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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. 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.</description><subject>Abdomen</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biology</subject><subject>Biosynthesis</subject><subject>Buffers</subject><subject>Cadavers</subject><subject>Cell death</subject><subject>Cell Death - drug effects</subject><subject>Cold storage</subject><subject>Coronary vessels</subject><subject>Cryopreservation</subject><subject>Cytochrome</subject><subject>Disease</subject><subject>Electron transport</subject><subject>Electron Transport - drug effects</subject><subject>Electron transport chain</subject><subject>Hogs</subject><subject>In Situ Nick-End Labeling</subject><subject>Ischemia</subject><subject>Kidney transplantation</subject><subject>Kidney Tubules - drug effects</subject><subject>Kidney Tubules - pathology</subject><subject>Kidneys</subject><subject>Laboratory animals</subject><subject>Male</subject><subject>Medicine</subject><subject>Mitochondria</subject><subject>Mitochondria - 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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. 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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