title: Renal tight junction proteins are decreased in cisplatin-induced nephrotoxicity in rats.
abstract: Cisplatin (CP) is an antineoplastic agent that induces nephrotoxicity and oxidative stress. It is unknown whether renal tight junction (TJ) proteins expression and localization are modified in CP-induced nephrotoxicity.
  
  
  OBJECTIVE
  To study if the expression of the TJ proteins occludin, claudin-2, claudin-5 and zonula occludens-1 (ZO-1) is modified in rats with CP-induced nephrotoxicity.
  
  
  METHODS
  Male Wistar rats (n = 5/group) were injected with saline solution (V group), and the other group (CP group) was injected with a single dose of saline solution and CP (7.5 mg/kg i.p.). Rats were sacrificed 72 h after CP injection and blood, and 24-h urine samples were collected. Several plasma and urinary injury biomarkers as well as renal histopathology lesions, oxidative and nitrosative stress markers were evaluated, and protein levels of ocludin, claudin-2, claudin-5, ZO-1 were measured by Western blot. Statistically significant changes noted with different p < 0.05 versus V.
  
  
  RESULTS
  Nephrotoxicity was evident by histological alterations, glycosuria, decrease in creatinine clearance, increase in fractional excretion of sodium, serum creatinine and kidney injury molecule-1. These changes were associated with oxidative/nitrosative stress (increased renal abundance of 3-nitrotyrosine and protein kinase Cβ2 and decreased renal expression of nuclear factor-erythroid-2-related factor 2) and decreased activity of antioxidant enzymes. Finally, it was found that CP-induced renal damage was associated with decreased renal expression of occludin and claudin-2.
  
  
  CONCLUSIONS
  CP altered the TJ proteins expression and localization in the proximal tubule that was associated with oxidative/nitrosative stress.
authors: Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM) , University City, Mexico D.F. , Mexico .
authors: Joyce
authors: J
authors: Trujillo
authors: Eduardo
authors: E
authors: Molina-Jijón
authors: Omar Noel
authors: ON
authors: Medina-Campos
authors: Rafael
authors: R
authors: Rodríguez-Muñoz
authors: José Luis
authors: JL
authors: Reyes
authors: María L
authors: ML
authors: Loredo
authors: Edilia
authors: E
authors: Tapia
authors: Laura Gabriela
authors: LG
authors: Sánchez-Lozada
authors: Diana
authors: D
authors: Barrera-Oviedo
authors: José
authors: J
authors: Pedraza-Chaverri
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015153:Blotting, Western; D002945:Cisplatin / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011506:Proteins; D002945:Cisplatin
keywords: Cisplatin; claudins; nitrotyrosine; occludin; oxidative stress; tight junction proteins