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

Nanomedicine (Lond). 2018 Jun;13(11):1267-1284. doi: 10.2217/nnm-2017-0387.

Abstract

Aim: As a first study in literature, to investigate concentration-dependent (0-400 μg/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.

Keywords: albumin; primary rat hepatocytes; reactive oxygen species (ROS); superparamagnetic iron oxide nanoparticles (SPION); urea.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Ferric Compounds / adverse effects
  • Ferric Compounds / chemistry
  • Ferric Compounds / pharmacology*
  • Hepatocytes / drug effects*
  • Liver / drug effects
  • Magnetite Nanoparticles / adverse effects
  • Magnetite Nanoparticles / chemistry*
  • Oxidative Stress / drug effects*
  • Primary Cell Culture
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • Ferric Compounds
  • Magnetite Nanoparticles
  • Reactive Oxygen Species
  • ferric oxide