title: Recovery from ischemic acute kidney injury by spironolactone administration.
abstract: BACKGROUND
  Prophylactic mineralocorticoid receptor (MR) antagonism with spironolactone (Sp) in rats completely prevents renal damage induced by ischemia. Because acute renal ischemia cannot typically be predicted, this study was designed to investigate whether Sp could prevent renal injury after an ischemic/reperfusion insult.
  
  
  METHODS
  Six groups of male Wistar rats were studied: rats that received a sham abdominal operation (S); rats that underwent 20 min of ischemia and reperfusion for 24 h (I/R) and four groups of rats treated with Sp (20 mg/kg) 0, 3, 6 or 9 h after ischemia.
  
  
  RESULTS
  As expected, I/R resulted in renal dysfunction characterized by a fall in renal blood flow and glomerular filtration rate and severe tubular injury which was confirmed by a significant increase in tubular damage biomarkers including kidney injury molecule-1, heat shock protein 72 and urinary protein excretion. The renal injury induced by I/R was in part due to Rho-kinase, endothelin and angiotensin II type 1 receptor upregulation. Interestingly, Sp administration at 0 and 3 h after ischemia completely reversed and prevented the damage induced by I/R. The protection induced by Sp given 6 h after ischemia was partial, but no protection was observed by administering Sp 9 h after ischemia.
  
  
  CONCLUSIONS
  Our results show that MR antagonism administered, either immediately or 3 h after I/R, effectively prevented ischemic acute renal injury, indicating that spironolactone is a promising agent for preventing acute kidney injury once an ischemic insult has occurred.
authors.affiliation: Unidad de Fisiología Molecular, Departamento de Medicina Genómica, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Katy
authors.initials: K
authors.lastname: Sánchez-Pozos
authors.forename: Jonatan
authors.initials: J
authors.lastname: Barrera-Chimal
authors.forename: Juan
authors.initials: J
authors.lastname: Garzón-Muvdi
authors.forename: Rosalba
authors.initials: R
authors.lastname: Pérez-Villalva
authors.forename: Roxana
authors.initials: R
authors.lastname: Rodríguez-Romo
authors.forename: Cristino
authors.initials: C
authors.lastname: Cruz
authors.forename: Gerardo
authors.initials: G
authors.lastname: Gamba
authors.forename: Norma A
authors.initials: NA
authors.lastname: Bobadilla
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D000450:Aldosterone / Q000097:blood; D000818:Animals; D004334:Drug Administration Schedule; D050884:HSP72 Heat-Shock Proteins / Q000652:urine; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013148:Spironolactone / Q000008:administration & dosage*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D050884:HSP72 Heat-Shock Proteins; D000451:Mineralocorticoid Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D013148:Spironolactone; D000450:Aldosterone