Iodixanol induces apoptotic and antiproliferative effects but no necrotic cell death in renal proximal tubular cells in vitro.

PURPOSE: To evaluate the cytotoxic effects of the iso-osmolar contrast medium iodixanol on renal tubular cell cultures. MATERIALS AND METHODS: LLC-PK1 cells were incubated with iodixanol and isotonic NaCl (18.75 - 75 mg I/ml, 1 - 24 hours). Cell death was assessed by the trypan blue exclusion test. To assess apoptosis, mononucleosomes and oligonucleosomes of cell lysates were determined. Measurement of BrdU (5-bromo-2’-deoxyuridine) incorporation into the DNA was used for the quantification of cell proliferation. RESULTS: Iodixanol did not induce any significant increase in the number of necrotic cells (8 % and 9 % at 37.5 and 75 mg I/ml vs. 8 % for control, p > 0.05). In contrast, iodixanol significantly increased the number of oligonucleosomes indicating induction of apoptosis (125 ± 4 % of control, p < 0.05). Iodixanol induced a significant, dose- and time-dependent inhibition of BrdU incorporation indicating the inhibition of cell proliferation (92 ± 2 % and 79 ± 2 % of control at 18.75 and 37.5 mg I/ml, p < 0.001). CONCLUSION: Apoptosis plus an antiproliferative effect of iodixanol without cell necrosis contribute to the renal tubular toxicity of iodixanol.