Inflammogenic effect of polyacrylic acid in rat lung following intratracheal instillation

Chinatsu Nishida; Taisuke Tomonaga; Hiroto Izumi; Ke-Yong Wang; Hidenori Higashi; Toru Ishidao; Jun-Ichi Takeshita; Ryohei Ono; Kazuki Sumiya; Shota Fujii; Shinichi Mochizuki; Kazuo Sakurai; Kei Yamasaki; Kazuhiro Yatera; Yasuo Morimoto

doi:10.1186/s12989-022-00448-z

Inflammogenic effect of polyacrylic acid in rat lung following intratracheal instillation

Part Fibre Toxicol. 2022 Jan 21;19(1):8. doi: 10.1186/s12989-022-00448-z.

Authors

Affiliations

¹ Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan. 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
² Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan. 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
³ Shared-Use Research Center, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
⁴ Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
⁵ Department of Environmental Management, School of Health Sciences, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
⁶ Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan. 16-1 Onogawa, Tsukuba, Ibaraki, 305-8569, Japan.
⁷ Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka, 808-0135, Japan.
⁸ Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan. 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan. yasuom@med.uoeh-u.ac.jp.

Abstract

Background: Some organic chemicals are known to cause allergic disorders such as bronchial asthma and hypersensitivity pneumonitis, and it has been considered that they do not cause irreversible pulmonary fibrosis. It has recently been reported, however, that cross-linked acrylic acid-based polymer, an organic chemical, might cause serious interstitial lung diseases, including pulmonary fibrosis. We investigated whether or not intratracheal instillation exposure to cross-linked polyacrylic acid (CL-PAA) can cause lung disorder in rats.

Methods: Male F344 rats were intratracheally instilled with dispersed CL-PAA at low (0.2 mg/rat) and high (1.0 mg/rat) doses, and were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure to examine inflammatory and fibrotic responses and related gene expressions in the lungs. Rat lungs exposed to crystalline silica, asbestos (chrysotile), and NiO and CeO₂ nanoparticles were used as comparators.

Results: Persistent increases in total cell count, neutrophil count and neutrophil percentage, and in the concentration of the cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2 and C-X-C motif chemokine 5 (CXCL5), which correlated with lung tissue gene expression, were observed in bronchoalveolar lavage fluid (BALF) from 3 days until at least 1 month following CL-PAA intratracheal instillation. Persistent increases in heme oxygenase-1 (HO-1) in the lung tissue were also observed from 3 days to 6 months after exposure. Histopathological findings of the lungs demonstrated that extensive inflammation at 3 days was greater than that in exposure to silica, NiO nanoparticles and CeO₂ nanoparticles, and equal to or greater than that in asbestos (chrysotile) exposure, and the inflammation continued until 1 month. Fibrotic changes also progressed after 1 month postexposure.

Conclusion: Our results suggested that CL-PAA potentially causes strong neutrophil inflammation in the rat and human lung.

Keywords: Cross-linked polyacrylic acid (CL-PAA); Organic chemicals; Pulmonary toxicity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acrylic Resins*
Animals
Bronchoalveolar Lavage Fluid
Lung*
Male
Rats
Rats, Inbred F344

Substances

Acrylic Resins
carbopol 940