Inflammogenic effect of polyacrylic acid in rat lung following intratracheal instillation

• Published in: Particle and fibre toxicology Vol. 19; no. 1; pp. 8 - 17
• Main Authors: Nishida, Chinatsu, Tomonaga, Taisuke, Izumi, Hiroto, Wang, Ke-Yong, Higashi, Hidenori, Ishidao, Toru, Takeshita, Jun-ichi, Ono, Ryohei, Sumiya, Kazuki, Fujii, Shota, Mochizuki, Shinichi, Sakurai, Kazuo, Yamasaki, Kei, Yatera, Kazuhiro, Morimoto, Yasuo
• Format: Journal Article
• Language: English
• Published: London BioMed Central 21.01.2022; BioMed Central Ltd; BMC
• Subjects: Acids; Acrylic acid; Acrylic Resins; Aerosols; Alveolitis; Animals; Asbestos; Asthma; Biomedical and Life Sciences; Biomedicine; Bronchoalveolar Lavage Fluid; Bronchus; Cerium oxides; Chemokines; Chrysotile; Comparators; Cross-linked polyacrylic acid (CL-PAA); Crosslinking; Cytokines; Development and progression; Dust; Environmental Health; Exposure; Fibrosis; Gene expression; Health aspects; Heme; Heme oxygenase (decyclizing); Hypersensitivity; Inflammation; Leukocytes (neutrophilic); Lung; Lung diseases; Lungs; Male; Medical prognosis; Nanoparticles; Nanotechnology; Neutrophils; Nickel oxides; Organic chemicals; Organic chemistry; Oxidative stress; Oxygenase; Pharmacology/Toxicology; Pneumology/Respiratory System; Pneumonitis; Polyacrylic acid; Polymers; Public Health; Pulmonary fibrosis; Pulmonary toxicity; Rats; Rats, Inbred F344; Risk factors; Silica; Silicon dioxide; Trachea; Working groups; Japan; Cross-linked polyacrylic acid (CL-PAA); Pulmonary toxicity; Organic chemicals
• ISSN: 1743-8977; 1743-8977
• DOI: 10.1186/s12989-022-00448-z

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 CeO 2 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 CeO 2 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.