Protection against renal ischemia-reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ

Redox Biol. 2015 Aug;5:163-168. doi: 10.1016/j.redox.2015.04.008. Epub 2015 Apr 29.

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.

Keywords: Ischemia–reperfusion injury; Kidney; MitoQ; Mitochondria; Mitochondria targeted antioxidants; Oxidative damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Creatinine / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / metabolism*
  • Organophosphorus Compounds / pharmacology*
  • Organophosphorus Compounds / therapeutic use
  • Oxidative Stress / drug effects*
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / pharmacology
  • Ubiquinone / therapeutic use

Substances

  • 10-(6'-ubiquinonyl)decyltriphenylphosphonium bromide
  • Antioxidants
  • Organophosphorus Compounds
  • Ubiquinone
  • Creatinine