title: Effects of the radiocontrast agent iodixanol on endothelial cell morphology and function.
abstract: Iodinated radiocontrast media (RCM) are usually well tolerated, but their large and increasing use renders their toxicity a relevant problem, especially in high risk patients. The aim of the study was to investigate the possible toxic or activating effects of iodixanol on endothelial cells (EC) and the putative in vitro protective action of N-acetylcysteine and rosuvastatin. Morphology, oxidative status, redistribution of heat-shock protein 60 and secretion of proinflammatory products were studied in cultured human EC through confocal microscopy, immunofluorescence and immuno-enzymatic methods. EC reacted to iodixanol with shrinking and bulging, increase in intracellular oxidation and translocation of Heat Shock Protein 60 to the cell membrane. The secretion of proinflammatory products was strongly stimulated by sequential incubation of EC with iodixanol and TNFα (p<0.00001 for all tested molecules, namely TNFα, IL-8, sVCAM-1, MCP-1, and IL-6). N-acetylcysteine prevented morphologic and oxidative derangements, and significantly reduced proinflammatory product secretion (P range<0.0001 to<0.00001 for TNFα, VCAM-1, MCP-1, and IL-6); rosuvastatin inhibited morphology and oxidative modifications only. Our data help clarifying the mechanisms of early and late toxicity of RCM and support the use of anti-oxidant and anti-inflammatory agents for optimization of radiological procedures in high risk patients.
authors.affiliation: Dip.to di Clinica Medica, Nefrologia e Scienze della Prevenzione, Università degli Studi di Parma, Parma, Italy. nicoletta.ronda@unipr.it
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ronda
authors.forename: Francesco
authors.initials: F
authors.lastname: Potì
authors.forename: Alessandra
authors.initials: A
authors.lastname: Palmisano
authors.forename: Rita
authors.initials: R
authors.lastname: Gatti
authors.forename: Guido
authors.initials: G
authors.lastname: Orlandini
authors.forename: Umberto
authors.initials: U
authors.lastname: Maggiore
authors.forename: Aderville
authors.initials: A
authors.lastname: Cabassi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Regolisti
authors.forename: Enrico
authors.initials: E
authors.lastname: Fiaccadori
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000378:metabolism; D003287:Contrast Media / Q000008:administration & dosage / Q000633:toxicity*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D005464:Fluorobenzenes / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D018613:Microscopy, Confocal; D018384:Oxidative Stress / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology; D014283:Triiodobenzoic Acids / Q000008:administration & dosage / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D018834:Chaperonin 60; D003287:Contrast Media; D005464:Fluorobenzenes; D011743:Pyrimidines; D013449:Sulfonamides; D014283:Triiodobenzoic Acids; D014409:Tumor Necrosis Factor-alpha; D000068718:Rosuvastatin Calcium; C044834:iodixanol; D000111:Acetylcysteine