Iodixanol induces apoptotic and antiproliferative effects but no necrotic cell death in renal proximal tubular cells in vitro.
OBJECTIVE
To evaluate the cytotoxic effects of the iso-osmolar contrast medium iodixanol on renal tubular cell cultures.


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).


CONCLUSIONS
Apoptosis plus an antiproliferative effect of iodixanol without cell necrosis contribute to the renal tubular toxicity of iodixanol.
Heinrich
M C
MC
Radiologisches Institut, Universitätsklinikum Erlangen.
Scheer
M
M
Heckmann
M
M
Kuefner
M A
MA
Uder
M
M
D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003287:Contrast Media / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects*; D009336:Necrosis / Q000139:chemically induced; D014283:Triiodobenzoic Acids / Q000633:toxicity*
D003287:Contrast Media; D014283:Triiodobenzoic Acids; C044834:iodixanol