title: Systemic inflammation and oxidative stress in hemodialysis patients are associated with down-regulation of Nrf2.
abstract: BACKGROUND
  Oxidative stress and inflammation are common features and the main mediators of progression of chronic kidney disease (CKD) and its cardiovascular complications. Under normal conditions, oxidative stress activates the transcription factor, nuclear factor E2-related factor 2 (Nrf2), which is the master regulator of genes encoding antioxidant and detoxifying enzymes and related proteins. The available data on expression of Nrf2 and its key target gene products in CKD patients is limited. We therefore investigated this topic in a group of CKD patients on hemodialysis.
  
  
  METHODS
  Twenty adult hemodialysis (HD) patients (aged 54.9 ± 15.2 years) and 11 healthy individuals (aged 50.9 ± 8.0 years) were enrolled. Peripheral blood mononuclear cells (PBMC) were isolated and processed for expression of nuclear factor-κB (NF-κB), Nrf2, heme oxygenase-1 and NADPH: quinoneoxidoreductase 1 (NQO1) by quantitative real-time polymerase chain reaction and western blot analysis. Plasma malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) levels were measured.
  
  
  RESULTS
  Peripheral blood mononuclear cells from HD patients had significantly lower NQO1 and Nrf2 mRNA expressions (0.58 ± 0.35 vs. 1.13 ± 0.64, p = 0.005), and significantly higher NF-κB expression (2.18 ± 0.8 vs. 1.04 ± 0.22, p = 0.0001) compared to the healthy individuals. The NF-κB expression was inversely correlated with Nrf2 levels (r = -0.54, p < 0.01) in CKD patients. Plasma MDA and TNF-α levels were significantly higher in CKD patients than in the healthy individuals.
  
  
  CONCLUSIONS
  Up-regulation of NFκB in the CKD patients' PBMC is coupled to down-regulation of Nrf2 and NQO1 expression. These observations are consistent with recent findings in CKD animals and point to the contribution of the impaired Nrf2 system in the pathogenesis of oxidative stress and inflammation in hemodialysis patients.
authors.affiliation: Graduate Program in Cardiovascular Sciences, Universidade Federal Fluminense (UFF), Niterói, RJ, Brazil, lilianapedruzzi@yahoo.com.br.
authors.forename: Liliana M
authors.initials: LM
authors.lastname: Pedruzzi
authors.forename: Ludmila F M F
authors.initials: LF
authors.lastname: Cardozo
authors.forename: Julio B
authors.initials: JB
authors.lastname: Daleprane
authors.forename: Milena B
authors.initials: MB
authors.lastname: Stockler-Pinto
authors.forename: Elisa B
authors.initials: EB
authors.lastname: Monteiro
authors.forename: Maurilo
authors.initials: M
authors.lastname: Leite
authors.forename: Nosratola D
authors.initials: ND
authors.lastname: Vaziri
authors.forename: Denise
authors.initials: D
authors.lastname: Mafra
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D006435:Renal Dialysis / Q000009:adverse effects*; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human