title: Ascorbic acid improves renal microcirculatory oxygenation in a rat model of renal I/R injury.
abstract: OBJECTIVE
  Acute kidney injury (AKI) is a clinical condition associated with a degree of morbidity and mortality despite supportive care, and ischemia/reperfusion injury (I/R) is one of the main causes of AKI. The pathophysiology of I/R injury is a complex cascade of events including the release of free oxygen radicals followed by damage to proteins, lipids, mitochondria, and deranged tissue oxygenation. In this study, we investigated whether the antioxidant ascorbic acid would be able to largely prevent oxidative stress and consequently, reduce I/R-related injury to the kidneys in terms of oxygenation, inflammation, and renal failure.
  
  
  METHODS
  Rats were divided into three groups (n= 6/group): (1) a time control group; (2) a group subjected to renal ischemia for 60 min by high aortic occlusion followed by 2 h of reperfusion (I/R); and (3) a group subjected to I/R and treated with an i.v. 100 mg/kg bolus ascorbic acid 15 min before ischemia and continuous infusion of 50 mg/kg/hour for 2 h during reperfusion (I/R + AA). We measured renal tissue oxidative stress, microvascular oxygenation, renal oxygen delivery and consumption, and renal expression of inflammatory and injury markers.
  
  
  RESULTS
  We demonstrated that aortic clamping and release resulted in increased oxidative stress and inflammation that was associated with a significant fall in systemic and renal hemodynamics and oxygenation parameters. The treatment of ascorbic acid completely abrogated oxidative stress and inflammatory parameters. However, it only partly improved microcirculatory oxygenation and was without any effect on anuria.
  
  
  CONCLUSIONS
  The ascorbic acid treatment partly improves microcirculatory oxygenation and prevents oxidative stress without restoring urine output in a severe I/R model of AKI.
authors.affiliation: Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Bulent
authors.initials: B
authors.lastname: Ergin
authors.affiliation: Laboratory of Experimental Anesthesiology and Intensive Care, Department of Anesthesiology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Coert J
authors.initials: CJ
authors.lastname: Zuurbier
authors.affiliation: Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: Bezemer
authors.affiliation: Department of Biology, Faculty of Science, University of Istanbul, Istanbul, Turkey.
authors.forename: Asli
authors.initials: A
authors.lastname: Kandil
authors.affiliation: Department of Anesthesiology, St. Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands.
authors.forename: Emre
authors.initials: E
authors.lastname: Almac
authors.affiliation: Department of Biology, Faculty of Science, University of Istanbul, Istanbul, Turkey.
authors.forename: Cihan
authors.initials: C
authors.lastname: Demirci
authors.affiliation: Department of Translational Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Can
authors.initials: C
authors.lastname: Ince
keywords: Ischemia/Reperfusion; acute kidney injury; ascorbic acid; oxidative stress; oxygenation