Inflammogenic effect of polyacrylic acid in rat lung following intratracheal instillation

Our plain-English summary of Inflammogenic effect of polyacrylic acid in rat lung following intratracheal instillation, by C. Nishida, T. Tomonaga, H. Izumi, et al (Particle and Fibre Toxicology, 2022).

The study

• Authors: C. Nishida, T. Tomonaga, H. Izumi, K.Y. Wang, H. Higashi, T. Ishidao, J.I. Takeshita, R. Ono, K. Sumiya, S. Fujii, S. Mochizuki, K. Sakurai, K. Yamasaki, K. Yatera, Y. Morimoto
• Journal: Particle and Fibre Toxicology
• Published: 2022;19(1):8
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2022. The Author(s).

In plain English

This was an animal experiment in Japan testing whether cross-linked polyacrylic acid (CL-PAA), a powdered organic polymer, harms the lungs. Male F344 rats received one dose of 0.2 mg or 1.0 mg of CL-PAA placed directly into the windpipe (intratracheal instillation). Control rats received distilled water. Five rats per group were examined at each of five times, from 3 days to 6 months. Fluid washed from the lungs showed significantly raised total cell counts from 3 days to 1 month, and raised neutrophils (an inflammatory white cell) up to 3 months. A marker of oxidative stress, HO-1, stayed raised in lung tissue. Under the microscope, inflammation at 3 days was greater than in lungs given crystalline silica and equal to or greater than in lungs given asbestos (chrysotile), which were used as comparisons. Scarring (fibrosis) appeared from 1 month. At 3 months it scored more severe than with silica or chrysotile. The authors concluded that CL-PAA has a high potential to cause lung disorder. They said inhalation studies are needed because instillation is not a natural route of exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: single intratracheal instillation in rats, with a distilled-water control group and comparison lungs exposed to crystalline silica, chrysotile asbestos, and NiO and CeO2 nanoparticles
• Who was studied: Male Fischer 344 rats from Charles River Laboratories (Kanagawa, Japan), dosed at 12 weeks old; 5 rats in each exposure and control group at each time point (3 days, 1 week, 1 month, 3 months, 6 months)
• Exposure: Cross-linked polyacrylic acid (CL-PAA) suspended in distilled water, given at 0.2 mg (0.8 mg/kg body weight) or 1.0 mg (4.0 mg/kg body weight). Comparison lungs received 1.0 mg of crystalline silica, asbestos (chrysotile), NiO nanoparticles or CeO2 nanoparticles.
• Main results:
  • Total cells in lung lavage fluid were significantly increased in both the 0.2 mg and 1.0 mg CL-PAA groups, compared with controls, from 3 days to 1 month after exposure
  • Neutrophil number and neutrophil percentage in lavage fluid were significantly increased from 3 days to 3 months after exposure
  • The neutrophil-attracting chemokines CINC-1, CINC-2 and CXCL5 in lavage fluid increased persistently and dose-dependently from 3 days until 1 month after exposure
  • HO-1, an oxidative stress protein, was persistently and significantly increased in CL-PAA-exposed lung tissue during the observation period
  • In the gene analysis at 1 month in the 1.0 mg group (RNA pooled from five rats per group), the most upregulated gene, CXCL5, was 69.02-fold higher than in controls
  • Lung inflammation at 3 days after CL-PAA was greater than after silica (and greater than after NiO and CeO2 nanoparticles)
  • Lung inflammation at 3 days after CL-PAA was equal to or greater than after asbestos (chrysotile)
  • Inflammation persisted at 1 month without granulomas or giant cells, and alveolar fibrosis was seen from 1 month
  • At 3 months, fibrosis scores (Ashcroft score) after 1.0 mg CL-PAA were higher than after 1.0 mg crystalline silica or 1.0 mg asbestos (chrysotile)
  • Micro-CT (in 3 of 5 animals per group) showed lung infiltration at 3 days and 1 month that improved by 3 months
• The authors' conclusion: The authors concluded that their results suggest CL-PAA has a high potential to induce lung disorder
• Limitations the authors state:
  • Intratracheal instillation is not a natural (physiological) exposure route; inhalation studies are needed to establish whether CL-PAA exposure causes lung inflammation and fibrosis

Topics

Medical terms in this study, explained in our Lexicon: Pneumonitis, Pulmonary Fibrosis, Interstitial Lung Disease, Crystalline, Chrysotile, Cytokine, Bronchoalveolar Lavage (BAL), Inflammation.

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