title: Protection against renal ischemia-reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ.
abstract: Ischemia-reperfusion (IR) injury to the kidney occurs in a range of clinically important scenarios including hypotension, sepsis and in surgical procedures such as cardiac bypass surgery and kidney transplantation, leading to acute kidney injury (AKI). Mitochondrial oxidative damage is a significant contributor to the early phases of IR injury and may initiate a damaging inflammatory response. Here we assessed whether the mitochondria targeted antioxidant MitoQ could decrease oxidative damage during IR injury and thereby protect kidney function. To do this we exposed kidneys in mice to in vivo ischemia by bilaterally occluding the renal vessels followed by reperfusion for up to 24h. This caused renal dysfunction, measured by decreased creatinine clearance, and increased markers of oxidative damage. Administering MitoQ to the mice intravenously 15 min prior to ischemia protected the kidney from damage and dysfunction. These data indicate that mitochondrial oxidative damage contributes to kidney IR injury and that mitochondria targeted antioxidants such as MitoQ are potential therapies for renal dysfunction due to IR injury.
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, Cambridge BioMedical Campus, Hills Road, Cambridge CB2 0XY, UK.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Dare
authors.affiliation: Department of Surgery, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
authors.forename: Eleanor A
authors.initials: EA
authors.lastname: Bolton
authors.affiliation: Department of Surgery, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Pettigrew
authors.affiliation: Department of Surgery, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Bradley
authors.affiliation: Department of Surgery, University of Cambridge, NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
authors.forename: Kourosh
authors.initials: K
authors.lastname: Saeb-Parsy
authors.affiliation: Medical Research Council Mitochondrial Biology Unit, Cambridge BioMedical Campus, Hills Road, Cambridge CB2 0XY, UK. Electronic address: mpm@mrc-mbu.cam.ac.uk.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Murphy
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D003404:Creatinine / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D009943:Organophosphorus Compounds; D014451:Ubiquinone; C429014:mitoquinone; D003404:Creatinine
keywords: Ischemia–reperfusion injury; Kidney; MitoQ; Mitochondria; Mitochondria targeted antioxidants; Oxidative damage