title: Cytotoxic effects of ionic high-osmolar, nonionic monomeric, and nonionic iso-osmolar dimeric iodinated contrast media on renal tubular cells in vitro.
abstract: OBJECTIVE
  To compare the cytotoxic effects of dimeric and monomeric iodinated contrast media on renal tubular cells in vitro with regard to osmolality.
  
  
  METHODS
  LLC-PK1 cells were incubated with ioxithalamate, ioversol, iomeprol-300, iomeprol-150, iodixanol, iotrolan, and hyperosmolar mannitol solutions for 1-24 hours at concentrations from 18.75 to 150 mg of iodine per milliliter. Cytotoxic effects were assessed with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Data were analyzed with one-way analysis of variance; post hoc tests were performed.
  
  
  RESULTS
  At equal iodine concentrations, ioxithalamate showed stronger cytotoxic effects than did other contrast media (MTT conversion for ioxithalamate was 4% vs that for ioversol of 32%, that for iomeprol-300 of 34%, that for iodixanol of 40%, and that for iotrolan of 41% of undamaged control cells at 75 mg of iodine per milliliter, n = 61-90, P < .001); there was no significant difference between low-osmolar monomeric and iso-osmolar dimeric contrast media (P > .05). At equal molarity, dimeric contrast media induced significantly stronger cytotoxic effects than did low-osmolar monomeric contrast media (40% for iodixanol and 41% for iotrolan vs 64% for ioversol and 59% for iomeprol-300 at 98.5 mmol/L, n = 61-75, P < .001). At equimolar concentrations, both dimeric contrast media showed stronger cytotoxic effects than did iso-osmolar formulation of iomeprol-150 (51% for iodixanol and 50% for iotrolan vs 77% for iomeprol-150 at 98.5 mmol/L, n = 35-40, P < .001). Mannitol solutions induced weaker cytotoxic effects than did corresponding contrast media compounds (74% for mannitol-520 vs 34% for iomeprol-300 and 41% for mannitol-1860 vs 4% for ioxithalamate, P < .001).
  
  
  CONCLUSIONS
  Besides hyperosmolality, direct cytotoxic effects of contrast media molecules contribute to their cytotoxic effects. Results of this study indicate that dimeric contrast media molecules have a greater potential for cytotoxic effects on proximal renal tubular cells in vitro than do monomeric contrast media molecules.
authors.affiliation: Department of Diagnostic Radiology, Division of Nephrology and Hypertension, University Hospital of Saarland, Homburg/Saar, Germany.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Heinrich
authors.forename: Martin K
authors.initials: MK
authors.lastname: Kuhlmann
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Grgic
authors.forename: Martina
authors.initials: M
authors.lastname: Heckmann
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kramann
authors.forename: Michael
authors.initials: M
authors.lastname: Uder
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003287:Contrast Media / Q000009:adverse effects*; D007479:Iopamidol / Q000009:adverse effects / Q000031:analogs & derivatives*; D007483:Iothalamic Acid / Q000009:adverse effects / Q000031:analogs & derivatives*; D008353:Mannitol / Q000009:adverse effects; D009994:Osmolar Concentration; D013552:Swine; D014283:Triiodobenzoic Acids / Q000009:adverse effects
chemical_list: D003287:Contrast Media; D014283:Triiodobenzoic Acids; D007483:Iothalamic Acid; C033300:iotrolan; C057937:iomeprol; D008353:Mannitol; C002587:ioxitalamic acid; C044834:iodixanol; D007479:Iopamidol; C054871:ioversol