title: Intravascular radiocontrast iodixanol increases permeability of proximal tubule epithelium: a possible mechanism of contrast-induced nephropathy.
abstract: OBJECTIVE
  To investigate the effect of Iodixanol on kidney proximal tubular cell line human kidney 2 (HK-2).
  
  
  METHODS
  The HK-2 cells were treated with Iodixanol. A Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay was used to evaluate apoptosis. Cell viability was measured by proliferation assay kit. Cell permeability changes were assessed by transwell assay and intercellular gaps measurement. Expression of claudin-2 was assessed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot.
  
  
  RESULTS
  Iodixanol reduced tubule cell viability (P < .01) but did not cause apoptosis. The intercellular gap formation (P < .01) and transwell (P < .05) assays revealed that cell permeability significantly increased after Iodixanol treatment of monolayer cells. Western blot and qRT-PCR showed significant upregulation of claudin-2 protein (P < .05) and messenger RNA expression (P < .01).
  
  
  CONCLUSIONS
  Our in vitro data do not support the hypothesis that direct kidney cell death from Iodixanol is a major mechanism of contrast-induced nephropathy (CIN). However, increased permeability of proximal tubule epithelium caused by Iodixanol may play an important role in CIN.
authors.affiliation: 1Department of Surgery, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Luyu
authors.initials: L
authors.lastname: Yao
authors.forename: Gopi K
authors.initials: GK
authors.lastname: Kolluru
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kevil
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D057167:Claudins / Q000235:genetics / Q000378:metabolism; D003287:Contrast Media / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010539:Permeability; D014283:Triiodobenzoic Acids / Q000633:toxicity*; D015854:Up-Regulation
chemical_list: C491875:CLDN2 protein, human; D057167:Claudins; D003287:Contrast Media; D014283:Triiodobenzoic Acids; C044834:iodixanol
keywords: contrast-induced nephropathy; iodixanol; permeability; proximal tubule epithelium