title: p53-Mediated oxidative stress and tubular injury in rats with glycerol-induced acute kidney injury.
abstract: OBJECTIVE
  p53 is a transcriptional factor that responds to severe cell damage promoting the transcription of proapoptotic and prooxidant genes. In this study, we evaluated the role of p53 activation in glycerol-induced acute kidney injury (Gly-AKI).
  
  
  METHODS
  Rats were treated with p53 inhibitor (pifithrin-α) in the moment we injected glycerol. Renal function, renal histology (HE), TUNEL labeling, cleaved caspase-3 staining, renal p53, Bax, PUMA, Bcl-2, p21 and survivin expressions, renal lipid and DNA oxidative markers, and the expression of antioxidant enzymes (Mn-SOD, HO-1, and NAD(P)H:quinone-oxidoreductase-1) were evaluated.
  
  
  RESULTS
  Gly-AKI rats showed an increased renal expression of phosphorylated-p53. The p53 inhibitor attenuated renal impairment and significantly reduced tubular injury. The expression of the oxidative markers was significantly reduced in treated rats. Proapoptotic and prooxidant proteins Bax and PUMA were overexpressed in Gly-AKI rats and reduced in treated rats. On the contrary, antiapoptotic Bcl-2, p21, and survivin showed a tendency to increase in treated rats. The antioxidant enzymes' expression remained elevated or increased in treated rats.
  
  
  CONCLUSIONS
  On the whole, p53 inhibition was protective in the short term. The oxidative stress subsided and the transcription tipped toward prosurvival genes; consequently tubular injury was attenuated in treated rats.
authors.affiliation: Department of Medicine, State University of Campinas, Brazil. ehomsi@aclnet.com.br
authors.forename: Eduardo
authors.initials: E
authors.lastname: Homsi
authors.forename: Sergio
authors.initials: S
authors.lastname: Mota da Silva
authors.forename: Silvano
authors.initials: S
authors.lastname: Machado de Brito
authors.forename: Elisa
authors.initials: E
authors.lastname: Bouçada Inácio Peixoto
authors.forename: Jose
authors.initials: J
authors.lastname: Butori Lopes de Faria
authors.forename: Patrícia
authors.initials: P
authors.lastname: Janino
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D052160:Benzothiazoles / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism* / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D014050:Toluene / Q000031:analogs & derivatives / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D052160:Benzothiazoles; D016159:Tumor Suppressor Protein p53; D014050:Toluene; C121565:pifithrin; D053148:Caspase 3; D005990:Glycerol