title: Selenium inhibits renal oxidation and inflammation but not acute kidney injury in an animal model of rhabdomyolysis.
abstract: Acute kidney injury (AKI) is a manifestation of rhabdomyolysis (RM). Extracellular myoglobin accumulating in the kidney after RM promotes oxidative damage, which is implicated in AKI.
  
  
  OBJECTIVE
  To test whether selenium (Se) supplementation diminishes AKI and improves renal function.
  
  
  RESULTS
  Dietary selenite increased Se in the renal cortex, as demonstrated by X-ray fluorescence microscopy. Experimental RM-stimulated AKI as judged by increased urinary protein/creatinine, clusterin, and kidney injury molecule-1 (KIM-1), decreased creatinine clearance (CCr), increased plasma urea, and damage to renal tubules. Concentrations of cholesterylester (hydro)peroxides and F₂-isoprostanes increased in plasma and renal tissues after RM, while aortic and renal cyclic guanidine monophosphate (cGMP; marker of nitric oxide (NO) bioavailability) decreased. Renal superoxide dismutase-1, phospho-P65, TNFα gene, MCP-1 protein, and the 3-chloro-tyrosine/tyrosine ratio (Cl-Tyr/Tyr; marker of neutrophil activation) all increased after RM. Dietary Se significantly decreased renal lipid oxidation, phospho-P65, TNFα gene expression, MCP-1 and Cl-Tyr/Tyr, improved NO bioavailability in aorta but not in the renal microvasculature, and inhibited proteinuria. However, CCr, plasma urea and creatinine, urinary clusterin, and histopathological assessment of AKI remained unchanged. Except for the Se++ group, renal angiotensin-receptor-1/2 gene/protein expression increased after RM with parallel increases in MEK1/2 inhibitor-sensitive MAPkinase (ERK) activity.
  
  
  METHODS
  We employed synchrotron radiation to identify Se distribution in kidneys, in addition to assessing reno-protection after RM.
  
  
  CONCLUSIONS
  Se treatment has some potential as a therapeutic for AKI as it inhibits oxidative damage and inflammation and decreases proteinuria, albeit histopathological changes to the kidney and some plasma and urinary markers of AKI remain unaffected after RM.
authors.affiliation: Discipline of Pathology, Redox Biology Group, Bosch Institute, The University of Adelaide, Australia.
authors.forename: Anu
authors.initials: A
authors.lastname: Shanu
authors.forename: Ludwig
authors.initials: L
authors.lastname: Groebler
authors.forename: Hyun Bo
authors.initials: HB
authors.lastname: Kim
authors.forename: Sarah
authors.initials: S
authors.lastname: Wood
authors.forename: Claire M
authors.initials: CM
authors.lastname: Weekley
authors.forename: Jade B
authors.initials: JB
authors.lastname: Aitken
authors.forename: Hugh H
authors.initials: HH
authors.lastname: Harris
authors.forename: Paul K
authors.initials: PK
authors.lastname: Witting
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology*; D000818:Animals; D019587:Dietary Supplements; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012206:Rhabdomyolysis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012643:Selenium / Q000008:administration & dosage / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D012643:Selenium