INTRODUCTION. Contrast-induced nephropathy represents the third highest cause of hospital-acquired acute renal failure. In this study we aimed to determine whether the use of iso-osmolar Iodixanol is less nephrotoxic than low-osmolar Iohexol and Iopamidol in cellular model.

MATERIALS AND METHODS. Xray-attenuation of Iohexol, Iopamidol and Iodixanol was assessed at equimolar Iodine concentrations. Human renal tubular cells were incubated with equally attenuating solutions of CM. Cytotoxicity was assessed by trypan blue testing, MTT-assay and AnnexinV/Propidium-Iodide assay to detect apoptosis and necrosis. ROS-production was assessed by DCF-assay and NADPH-oxidase activity was checked by chemiluminescence method.

RESULTS. Yielding the same Xray-attenuation, CM-cytotoxicity was assessed at equimolar Iodine concentrations. At trypan blue testing, there were more necrotic cells after incubation with 50, 100, 150 and 270mgI/mL of iohexol and iopamidol than after incubation with equal concentrations of iodixanol (p<0.005 among groups at each concentration). Iohexol and Iodixanol at 20 and 50mgI/mL induced comparable inhibition of MTT conversion with a dose-dependent effect, while Iopamidol showed a marked cytotoxic effect, as compared with Iodixanol (26.0_vs_54.9% at 20mgI/mL and 23.2_vs_36.8% at 50mgI/mL of undamaged control cells for Iohexol and Iodixanol, respectively; p<0.05). Moreover, both Iohexol and Iopamidol induced more necrosis and apoptosis than Iodixanol with a dose-dependent effect (Iodixanol vs Iopamidol: for necrosis 1.9_vs_1.1% at 20mgI/mL and 2.8_vs_0.9% at 50mgI/mL. p<0.05; for apoptosis 45.6_vs_36.9% at 20mgI/mL and 52.0_vs_40.0% at 50mgI/mL, p<0.05). ROS generation was higher for Iopamidol and Iohexol as compared with iodixanol (after 40min 21263±2124 and 8985±1601 vs 4430±801 AU at 20mgI/mL, p<0.05; 9844±1124 and 8113±101 vs 4076±601 AU at 50mgI/mL, p<0.05). NADPH-oxidase activity significantly increase after exposure to Iopamidol and Iohexol with a dosedependent effect, as compared with Iodixanol (27.6 and 50.5 vs 8.9% over the basal at 20mgI/dL, p<0.05; 50.5 and 71.1 vs 35.8% over the basal at 50mgI/dL, p<0.05).

CONCLUSION. At angiographic concentrations Iodixanol induces fewer cytotoxic effects on cultured tubular cells than Iohexol and Iopamidol by inducing lower amount NADPH-dependent ROS-generation.