The potentiation effect makes the difference: Non-toxic concentrations of ZnO nanoparticles enhance Cu nanoparticle toxicity in vitro

Abstract

• ZnONPs at non-toxic concentrations increased the toxicity of CuNPs in vitro.• ZnONPs of larger size provoked a stronger synergistic effect with CuNPs.• The synergistic effect was attributed to the particle fraction of ZnONPs. Here we examined whether the addition of a non-toxic concentration (6.25 μg/mL) of zinc oxide nanoparticles (ZnONPs: 19, 35 and 57 nm, respectively) modulates the cytotoxicity of copper nanoparticles (CuNPs, 63 nm in size) in the human hepatoma cell line HepG2. The cytotoxic effect of CuNPs on HepG2 cells was markedly enhanced by the ZnONPs, the largest ZnONPs causing the highest increase in toxicity. However, CuNPs cytotoxicity was not affected by co-incubation with medium containing only zinc ions, indicating the increase in toxicity might be attributed to the particle form of ZnONPs. Transmission electron microscopy (TEM) revealed the presence of CuNPs and ZnONPs inside the cells co-exposed to both types of NP and outflow of cytoplasm through the damaged cell membrane. Inductively coupled plasma mass spectrometry (ICP-MS) determined an increase in the concentration of zinc and a decrease in that of copper in co-exposed cells. On the basis of these results, we propose that accumulation of large numbers of ZnONPs in the cells alters cellular membranes and the cytotoxicity of CuNPs is increased. a b s t r a c t a r t i c l e i n f o

Mechanisms underlying the enhancement of toxicity caused by the coincubation of zinc oxide and copper nanoparticles in a fish hepatoma cell line

“…Absorbance was measured at 550 nm. We confirmed the absence of interferences of NPs with the wavelengths used to perform the measurements in the assays, as reported .…”

“…This effect could be associated with the previously mentioned in the section Cytotoxicity higher toxicity found in cells coexposed to 100‐nm ZnONPs and CuNPs in comparison with those coexposed to 25‐nm ZnONPs and CuNPs and could indicate an easier internalization of 100‐nm ZnONPs. In human cells (HepG2) we also found this size‐dependent cytotoxicity, but it could not be related to any increase in intracellular Zn levels . In any case, this difference suggests a species‐dependent difference in the mechanism of action/uptake.…”

Mechanisms of Toxicity of Ag Nanoparticles in Comparison to Bulk and Ionic Ag on Mussel Hemocytes and Gill Cells

“…Further studies are necessary to quantitatively identify the contribution of released Ag ions and Ag NPs to observed toxic effects. This question might be addressed by separating the dissolved fraction from the NPs and then exposing cells to the two fractions separately, as in Li et al [89] for ZnO NPs. Another possibility could be to assess the toxicity of NPs with a limited release of ions.…”

Ecotoxicity and genotoxicity of cyclophosphamide, ifosfamide, their metabolites/transformation products and their mixtures

“…It is also apparent that the dynamics of growth inhibition based on experimental data differ from predicted assumptions for concentrations >5 mg L À1 , suggesting the potentiation effect of a mixture containing parent compounds and their human metabolites/TPs. A potentiation effect is observed when the toxicity of a mixture of a non-toxic compound and a toxic compound results in an effect, higher than the determined toxicity of an individual toxic compound (Li et al, 2015). Such phenomenon, shown in Fig.…”