4.6 Article

Combination effect of nanoparticles on the acute pulmonary inflammogenic potential: additive effect and antagonistic effect

Journal

NANOTOXICOLOGY
Volume 15, Issue 2, Pages 276-288

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/17435390.2020.1862336

Keywords

Additive; antagonistic; lung inflammation; nanoparticle; reactive oxygen species

Funding

  1. National Research Foundation of Korea [2018K1A3A1A74065871, NRF-2019R1A2C1084489]
  2. Ministry of Food and Drug Safety of Korea [19172MFDS221]
  3. BB21thorn Project in 2019
  4. National Research Foundation of Korea [2018K1A3A1A74065871] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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The combined effect of different types of nanomaterials in human exposure is little known. Research shows that co-exposure of certain nanomaterials can lead to an increase in the percentage of neutrophils and enhanced potential for ROS generation. These effects vary depending on the specific combination of nanomaterials used.
The combination effect of co-exposed different types of nanomaterials is little known although humans are generally exposed to a mixture of nanomaterials from urban ultrafine particles or industrial nanomaterials. Herein, we evaluated the combined effect of nanoparticles (NPs) using three types of NPs in different inflammogenic categories: carbon black (CB), nickel oxide (NiO), and copper oxide (CuO). A single type of NPs or NPs in combination was intratracheally instilled into the lungs of rats and the bronchoalveolar lavage fluid (BALF) was analyzed at 24 h after instillation to evaluate the acute inflammogenic potential. The percentage of neutrophils in BALF was selected as a toxicity endpoint and the potential for reactive oxygen species (ROS) generation, dose-response of the combined effect, sequential treatment of CB and NiO, and uptake of NiO to alveolar macrophages after combined treatment of CB and NiO were evaluated for the mechanism of the combined effect. Co-exposure of CuO and NiO showed an additive effect on the percentage of neutrophils and ROS generation potential, which implies that the physicochemical properties of each NP are not influenced by the other type. While CB exerted an antagonistic effect on the percentage of neutrophils in combined treatment with CuO or NiO. The antagonistic effect of CB was due to the scavenging activity of the ROS generated by the CuO and NiO rather than the competition in cellular uptake to target cells (i.e. alveolar macrophages), which highlight the importance of the combined effect of NPs in the risk assessment.

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