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.
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