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Original Article

Barium sulfate micro- and nanoparticles as bioinert reference material in particle toxicology

, , , , , & show all
Pages 1492-1502 | Received 24 May 2016, Accepted 25 Jul 2016, Published online: 27 Sep 2016
 

Abstract

The inhalation of particles and their exposure to the bronchi and alveoli constitute a major public health risk. Chemical as well as particle-related properties are important factors for the biological response but are difficult to separate from each other. Barium sulfate is a completely inert chemical compound, therefore it is ideally suited to separate these two factors. The biological response of rat alveolar macrophages (NR8383) was analyzed after exposure to barium sulfate particles with three different diameters (40 nm, 270 nm, and 1.3 μm, respectively) for 24 h in vitro (particle concentrations from 12.5 to 200 μg mL1). The particles were colloidally stabilized as well as fluorescently-labeled by carboxymethylcellulose, conjugated with 6-aminofluorescein. All kinds of barium sulfate particles were efficiently taken up by NR8383 cells and found inside endo-lysosomes, but never in the cell nucleus. Neither an inflammatory nor a cytotoxic response was detected by the ability of dHL-60 and NR8383 cells to migrate towards a chemotactic gradient (conditioned media of NR8383 cells) and by the release of inflammatory mediators (CCL2, TNF-α, IL-6). The particles neither caused apoptosis (up to 200 μg mL1) nor necrosis (up to 100 μg mL1). As only adverse reaction, necrosis was found at a concentration of 200 μg mL1 of the largest barium sulfate particles (1.3 μm). Barium sulfate particles are ideally suited as bioinert control to study size-dependent effects such as uptake mechanisms of intracellular distributions of pure particles, especially in nanotoxicology.

Acknowledgements

We are grateful to Professor Peter Proksch, Institute of Pharmaceutical Biology, Düsseldorf, Germany, for mentoring Isabell Föhring née Schremmer's PhD project. We thank Dr Oleg Prymak, Essen, for X-ray powder diffraction analyses.

Conflict of interests

The authors declare that they have no conflicts of interest.

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