Dose-, treatment- and time-dependent toxicity of superparamagnetic iron oxide nanoparticles on primary rat hepatocytes

Aim: As a first study in literature, to investigate concentration-dependent (0-400 mu g/ml) and exposure-dependent (single dosing vs cumulative dosing) effects of superparamagnetic iron oxide nanoparticles (d = 10 nm) on primary rat hepatocytes in a time-dependent manner. Materials & methods: Sandwich-cultured hepatocyte model was used to evaluate viability, hepatocyte specific functions and reactive oxygen species level. Results: In terms of all parameters, generally statistically more significant effects were observed in a concentration- and time-dependent manner. In terms of hepatocyte-specific functions, cumulative dosing caused significantly (p < 0.05) more deleterious effects at 48th hour. Conclusion: A combination of various biomarkers should be employed for the evaluation of the effect of superparamagnetic iron oxide nanoparticles on liver, and each biomarker should be analyzed in a time- and exposure-dependent manner.