title: N-acetylcysteine as a potential strategy to attenuate the oxidative stress induced by uremic serum in the vascular system.
abstract: OBJECTIVE
  Chronic kidney disease (CKD) progression is accompanied by systemic oxidative stress, which contributes to an increase in the risk of cardiovascular diseases (CVDs). N-acetylcysteine (NAC) is among the most studied antioxidants, but its therapeutic benefits in CKD-associated CVDs remain controversial. Here, we investigated whether NAC could inhibit the oxidative stress induced by uremia in vitro and in vivo.
  
  
  METHODS
  Endothelial and smooth muscle cells were challenged with human uremic or non-uremic sera, and the effects of a pre-treatment with 2mM NAC were evaluated. Reactive oxygen species (ROS) production, protein oxidation and total glutathione/glutathione disulfide (tGSH/GSSG) ratios were measured. Five-sixths nephrectomized or sham-operated rats were orally treated (in the drinking water) with 60 mg/kg/day NAC or not treated for 53 days. Plasma cysteine/cystine reduction potential Eh(Cyss/2Cys) was determined as a novel marker of the systemic oxidative stress.
  
  
  RESULTS
  NAC inhibited all the determined oxidative stress parameters, likely by increasing the tGSH/GSSG ratio, in both cell lines exposed to uremic serum. Orally administered NAC attenuated the systemic oxidative stress in uremic rats.
  
  
  CONCLUSIONS
  The present results indicate that NAC, by preventing GSH depletion in vascular cells exposed to uremic serum and by attenuating the systemic oxidative stress during CKD progression, emerges as a potential strategy to prevent the oxidative stress induced by uremic toxicity in the vascular system.
authors.affiliation: Departamento de Patologia Básica, Universidade Federal do Paraná, Centro Politécnico, Curitiba 81531-980, Brazil.
authors.forename: Silvia D
authors.initials: SD
authors.lastname: Rodrigues
authors.affiliation: Departamento de Patologia Básica, Universidade Federal do Paraná, Centro Politécnico, Curitiba 81531-980, Brazil.
authors.forename: Karime C
authors.initials: KC
authors.lastname: França
authors.affiliation: Departamento de Patologia Básica, Universidade Federal do Paraná, Centro Politécnico, Curitiba 81531-980, Brazil.
authors.forename: Fernando T
authors.initials: FT
authors.lastname: Dallin
authors.affiliation: Laboratório de Fisiopatologia Renal, Faculdade de Medicina, Universidade de São Paulo, São Paulo 01246-903, Brazil.
authors.forename: Clarice K
authors.initials: CK
authors.lastname: Fujihara
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas,Universidade Federal do Paraná, Curitiba 80210-170, Brazil.
authors.forename: Aguinaldo J
authors.initials: AJ
authors.lastname: Nascimento
authors.affiliation: School of Medicine, Pontifícia Universidade Católica do Paraná, Rua Imaculada Conceição 1155, Curitiba 80215-901, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pecoits-Filho
authors.affiliation: Departamento de Patologia Básica, Universidade Federal do Paraná, Centro Politécnico, Curitiba 81531-980, Brazil. Electronic address: lia.nakao@ufpr.br.
authors.forename: Lia S
authors.initials: LS
authors.lastname: Nakao
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D009392:Nephrectomy; D018384:Oxidative Stress / Q000187:drug effects*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy; D014511:Uremia / Q000097:blood*
chemical_list: D015415:Biomarkers; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D005978:Glutathione; D000111:Acetylcysteine
keywords: N-acetylcysteine; Oxidative stress; Superoxide; Uremia; Vascular cells