The effects of pharyngeal aspiration-exposure to zinc oxide nanoparticles on pulmonary fibrosis induced by bleomycin in mice.
Wu-W; Ichihara-G; Tada-Oikawa-S; Suzuki-Y; Chang-J; Hashimoto-N; Hasegawa-Y; Porter-DW; Castranova-V; Gabazza-C; Gabazza-E; Ichihara-S
Toxicologist 2014 Mar; 138(1):522
The present study investigated underlying mechanism of pulmonary fibrosis caused by exposure to ZnO nanoparticles, in a mouse model of pulmonary fibrosis induced by bleomycin (BLM). The mouse model was completed by constant subcutaneous infusion of 100 mg/kg bleomycin sulphate using osmotic mini-pumps. Female C57BL/6Jcl mice were divided into BLM and non-BLM groups. In each group, two doses (10, 30 mg/mouse) of ZnO nanoparticles with primary diameter of 20 nm were delivered into the lungs through pharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) and the lungs were collected 10 days after administration under deep anesthesia. Exposure to ZnO nanoparticles dose-dependently increased the lungs weight. Histopathologically, slight and severe thickness was observed within interalveolar septum in low and high dose groups, respectively, which was accompanied by dose-dependent increase in total cells, macrophages, lymphocytes and neutrophils in BALF. The increase in total protein in BALF at high dose indicated increased permeability of air-blood barrier. IL-1 beta and MCP-1 in BALF were significantly higher in all BLM groups as opposed to the low levels in non-BLM groups, indicating lasting inflammation after exposure in BLM groups. Moreover, in BLM groups, ZnO nanoparticles led to dose-dependent increase in IL-1 beta and MCP-1, suggesting higher susceptibility to ZnO nanoparticles in this mouse model. This study suggested severer inflammation was caused by ZnO nanoparticles in the BLM mouse model of pulmonary fibrosis at the early stage.
Toxicology; Exposure-levels; Nanotechnology; Cytotoxicity; Cell-biology; Cell-function; Cellular-function; Pulmonary-disorders; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Respiratory-system-disorders; Fibrosis; Animals; Laboratory-animals; Models; Particulates; Lung; Lung-fibrosis; Lung-function; Lung-tissue; Lung-irritants
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona