The Degree of Cross-linking of Polyacrylic Acid Affects the Fibrogenicity in Rat Lungs

Overview

Journal Sci Rep

Date 2025 Jan 28

PMID 39875494

Authors

Taisuke Tomonaga

Hiroto Izumi

Chinatsu Nishida

Kazuma Sato

Yuiko Nakamura

Toshiki Morimoto

Yasuyuki Higashi

Ke-Yong Wang

Hidenori Higashi

Takuma Kojima

Kazuo Sakurai

Jun-Ichi Takeshita

Akihiro Moriyama

Kei Yamasaki

Kazuhiro Yatera

Yasuo Morimoto

Affiliations

Soon will be listed here.

Abstract

Polyacrylic acid (PAA) with different concentrations of cross-linker was instilled into the trachea of rats to examine the effect of PAA crosslink density on lung disorders. Methods: F344 rats were intratracheally exposed to low and high doses of PAA with cross-linker concentrations of 0.1, 1.0, and 5.0% (CL0.1%, CL1.0%, and CL5.0%, respectively). Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months after exposure. PAA with different cross-linker concentrations caused an increase in neutrophil influx, cytokine-induced neutrophils, and chemotactic factor (CINC) in bronchoalveolar lavage fluid (BALF) from 3 days to 1 week after instillation. Lactate dehydrogenase (LDH) activity in BALF and heme oxygenase-1 (HO-1) release in lung tissue were higher in the CL0.1% exposure group during the acute phase. Lung histopathological findings also showed that severe fibrotic changes induced by CL0.1% were greater than those observed in CL1.0% and CL5.0% exposure during the observation period. CL0.1% was associated with more severe lung fibrosis, and a decrease in lung fibrosis was observed with increasing cross-linker concentrations, suggesting that the cross-link density of PAA is a physicochemical feature that affects lung disorders.

References

McCauley L, Markin C, Hosmer D . An unexpected consequence of electronic cigarette use. Chest. 2012; 141(4):1110-1113. DOI: 10.1378/chest.11-1334. View

Castranova V, Vallyathan V . Silicosis and coal workers' pneumoconiosis. Environ Health Perspect. 2000; 108 Suppl 4:675-84. PMC: 1637684. DOI: 10.1289/ehp.00108s4675. View

Paek D, Koh Y, Park D, Cheong H, Do K, Lim C . Nationwide Study of Humidifier Disinfectant Lung Injury in South Korea, 1994-2011. Incidence and Dose-Response Relationships. Ann Am Thorac Soc. 2015; 12(12):1813-21. DOI: 10.1513/AnnalsATS.201504-221OC. View

Tomonaga T, Izumi H, Yoshiura Y, Myojo T, Oyabu T, Lee B . Usefulness of myeloperoxidase as a biomarker for the ranking of pulmonary toxicity of nanomaterials. Part Fibre Toxicol. 2018; 15(1):41. PMC: 6199695. DOI: 10.1186/s12989-018-0277-x. View

Morimoto Y, Izumi H, Yoshiura Y, Tomonaga T, Lee B, Okada T . Comparison of pulmonary inflammatory responses following intratracheal instillation and inhalation of nanoparticles. Nanotoxicology. 2015; 10(5):607-18. DOI: 10.3109/17435390.2015.1104740. View

Borm P, Driscoll K . Particles, inflammation and respiratory tract carcinogenesis. Toxicol Lett. 1996; 88(1-3):109-13. DOI: 10.1016/0378-4274(96)03725-3. View

Singh R, Ramarao P . Accumulated polymer degradation products as effector molecules in cytotoxicity of polymeric nanoparticles. Toxicol Sci. 2013; 136(1):131-43. DOI: 10.1093/toxsci/kft179. View

Kultz D . Hyperosmolality triggers oxidative damage in kidney cells. Proc Natl Acad Sci U S A. 2004; 101(25):9177-8. PMC: 438948. DOI: 10.1073/pnas.0403241101. View

Porter D, Hubbs A, Chen B, McKinney W, Mercer R, Wolfarth M . Acute pulmonary dose-responses to inhaled multi-walled carbon nanotubes. Nanotoxicology. 2012; 7(7):1179-94. PMC: 4687396. DOI: 10.3109/17435390.2012.719649. View

10.

Higashi Y, Nishida C, Tomonaga T, Izumi H, Kawai N, Morimoto T . Intratracheal instillation of polyacrylic acid induced pulmonary fibrosis with elevated transforming growth factor-β1 and connective tissue growth factor. Toxicology. 2024; 506:153845. DOI: 10.1016/j.tox.2024.153845. View

11.

Kishimoto T, Okamoto K, Koda S, Ono M, Umeda Y, Yamano S . Respiratory disease in workers handling cross-linked water-soluble acrylic acid polymer. PLoS One. 2023; 18(4):e0284837. PMC: 10120934. DOI: 10.1371/journal.pone.0284837. View

12.

Morimoto T, Izumi H, Tomonaga T, Nishida C, Kawai N, Higashi Y . The Effects of Endoplasmic Reticulum Stress via Intratracheal Instillation of Water-Soluble Acrylic Acid Polymer on the Lungs of Rats. Int J Mol Sci. 2024; 25(7). PMC: 11011863. DOI: 10.3390/ijms25073573. View

13.

de Souza Xavier Costa N, Junior G, Dos Santos Alemany A, Belotti L, Zati D, Frota Cavalcante M . Early and late pulmonary effects of nebulized LPS in mice: An acute lung injury model. PLoS One. 2017; 12(9):e0185474. PMC: 5617199. DOI: 10.1371/journal.pone.0185474. View

14.

Brocker C, Thompson D, Vasiliou V . The role of hyperosmotic stress in inflammation and disease. Biomol Concepts. 2012; 3(4):345-364. PMC: 3438915. DOI: 10.1515/bmc-2012-0001. View

15.

Thota D, Latham E . Case report of electronic cigarettes possibly associated with eosinophilic pneumonitis in a previously healthy active-duty sailor. J Emerg Med. 2014; 47(1):15-7. DOI: 10.1016/j.jemermed.2013.09.034. View

16.

Nishida C, Izumi H, Tomonaga T, Takeshita J, Wang K, Yamasaki K . Predictive Biomarkers for the Ranking of Pulmonary Toxicity of Nanomaterials. Nanomaterials (Basel). 2020; 10(10). PMC: 7602652. DOI: 10.3390/nano10102032. View

17.

Snyder-Talkington B, Dong C, Porter D, Ducatman B, Wolfarth M, Andrew M . Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study. J Toxicol Environ Health A. 2016; 79(8):352-66. PMC: 4899319. DOI: 10.1080/15287394.2016.1159635. View

18.

Takeda T, Yamano S, Goto Y, Hirai S, Furukawa Y, Kikuchi Y . Dose-response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats. Part Fibre Toxicol. 2022; 19(1):27. PMC: 8994297. DOI: 10.1186/s12989-022-00468-9. View

19.

Sumiya K, Matsunaga T, Tanaka M, Mochizuki S, Sakurai K . Oligo-DNA Stoichiometrically Binds β-1,3-Glucan with the Best Fit Length. Biomacromolecules. 2020; 21(12):4823-4834. DOI: 10.1021/acs.biomac.0c01038. View

20.

Nishida C, Tomonaga T, Izumi H, Wang K, Higashi H, Ishidao T . Inflammogenic effect of polyacrylic acid in rat lung following intratracheal instillation. Part Fibre Toxicol. 2022; 19(1):8. PMC: 8780717. DOI: 10.1186/s12989-022-00448-z. View