title: Priming prevent nephrotoxic acute renal failure through stimulation of antioxidant defense mechanism.
abstract: BACKGROUND
  Priming is the mechanism of protection induced by a previous exposition of a cell or organ to low or equal concentrations of a toxic substance.
  
  
  OBJECTIVE
  To analyze the mechanism of priming induced by the previous exposition to gentamicin in human proximal tubular cells and nephrotoxic acute renal failure (ARF).
  
  
  METHODS
  Wistar rats and tubular cells were exposed to gentamicin 2mM during 24h or 40 mg/kg during 3 days and after one rest week were exposed to the same concentration during 24h in cells and additional ten days in rats. The primed animals were compared to control rats receiving vehicle and GENTA animals treated with the gentamicin during the same period. Biochemical parameters were analyzed. The oxidative stress was analyzed by urinary hydroperoxides and carbonylated protein while antioxidant defense was studied by antioxidant activity of the plasma (FRAP), catalase, superoxide dismutase, heme-oxygenase 1 (HO-1) immunostaining and enzymatic activity in kidney. Necrosis, apoptosis, proliferation, endothelin 1 (ET-1) and HO-1 expression were studied in cells.
  
  
  RESULTS
  Priming of the animals inhibited the increase in creatinine, urea, sodium excretion and urinary protein induced by gentamicin. Bosentan, ET-1 receptor antagonist, and hemin, HO-1 inducer, potentiate the inhibition. The mechanism of protection was mediated by induction of the antioxidant enzymes HO-1, catalase and SOD activity and oxidative stress reduction. Priming inhibited cell death and induced proliferation through ET-1 production.
  
  
  CONCLUSIONS
  Priming is a persistent and multifactorial mechanism, the stimulation of the antioxidant defense could mimics partially the priming process and prevent the ARF.
authors.affiliation: Universidade Federal de São Paulo, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Duarte
authors.affiliation: Universidade Federal de São Paulo, Brazil.
authors.forename: Edson Andrade
authors.initials: EA
authors.lastname: Pessoa
authors.affiliation: Universidade Federal de São Paulo, Brazil.
authors.forename: Luciana Aparecida
authors.initials: LA
authors.lastname: Reis
authors.affiliation: Universidade Federal de São Paulo, Brazil.
authors.forename: Nestor
authors.initials: N
authors.lastname: Schor
authors.affiliation: Universidade Federal de São Paulo, Brazil.
authors.forename: Fernanda Teixeira
authors.initials: FT
authors.lastname: Borges
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D000975:Antioxidants / Q000502:physiology*; D002478:Cells, Cultured; D005839:Gentamicins / Q000008:administration & dosage; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000502:physiology*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D005839:Gentamicins