Effect of zirconium dioxide nanoparticles on glutathione peroxidase enzyme in PC12 and n2a cell lines

Iran J Pharm Res. 2014 Fall;13(4):1141-8.

Abstract

Today, special attention is paid to the use of zirconium dioxide nanoparticle (nano-ZrO2), a neutral bioceramic metal, particularly for drug and gene delivery in medicine. However, there are some reports implying that use of nano-ZrO2 is associated with cytotoxic effects like inhibiting the cell proliferation, DNA damage and apoptosis. In the present study, we examined whether nano-ZrO2 alters cell viability and glutathione peroxidase (GPx) activity in two neuronal cell lines. The PC12 and N2a cells were cultured in the absence or presence of varying concentrations (31.25-2000 µg/mL) of nano-ZrO2 for 12, 24 or 48 h. The cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and GPx activity was determined by quantifying the rate of oxidation of the reduced glutathione to the oxidized glutathione. Nano-ZrO2 caused a significant reduction in cell viability and GPx activity after 12, 24 and 48 h, as compared with control group. These effects were concentration dependent and started from 250 µg/mL. The present study demonstrated that nano-ZrO2, at concentrations of > 250 µg/mL, has antiproliferative effects via reducing the cell defense mechanism against oxidative stress.

Keywords: Zirconium dioxide nanoparticles; PC12 cell line; N2a cell line; Oxidative stress; Glutathione peroxidase enzyme.