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 l/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: lodixanol did not induce any significant increase in the number of necrotic cells (8% and 9% at 37.5 and 75 mg I/ml Ys. 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). lodixanol 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 l/ml, p < 0.001). Conclusion: Apoptosis plus an antiproliferative effect of iodixanol Without cell necrosis contribute to the renal tubular toxicity of iodixanol.