The degree of cross-linking of polyacrylic acid affects the fibrogenicity in rat lungs

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,...

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Main 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
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Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-87174-6
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author 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
author_facet 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
author_sort Taisuke Tomonaga
collection DOAJ
description 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.
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spelling doaj-art-bbf7ea3cb891462eb56e24529d619e8f2025-02-02T12:22:46ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-87174-6The degree of cross-linking of polyacrylic acid affects the fibrogenicity in rat lungsTaisuke Tomonaga0Hiroto Izumi1Chinatsu Nishida2Kazuma Sato3Yuiko Nakamura4Toshiki Morimoto5Yasuyuki Higashi6Ke-Yong Wang7Hidenori Higashi8Takuma Kojima9Kazuo Sakurai10Jun-ichi Takeshita11Akihiro Moriyama12Kei Yamasaki13Kazuhiro Yatera14Yasuo Morimoto15Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental HealthDepartment of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental HealthDepartment of Environmental Health Engineering, Institute of Industrial Ecological Sciences, University of Occupational and Environmental HealthDepartment of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental HealthDepartment of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental HealthDepartment of Respiratory Medicine, University of Occupational and Environmental HealthDepartment of Respiratory Medicine, University of Occupational and Environmental HealthShared-Use Research Center, School of Medicine, University of Occupational and Environmental HealthDepartment of Environmental Health Engineering, Institute of Industrial Ecological Sciences, University of Occupational and Environmental HealthDepartment of Chemistry and Biochemistry, The University of KitakyushuDepartment of Chemistry and Biochemistry, The University of KitakyushuResearch Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology (AIST)Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology (AIST)Department of Respiratory Medicine, University of Occupational and Environmental HealthDepartment of Respiratory Medicine, University of Occupational and Environmental HealthDepartment of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental HealthAbstract 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.https://doi.org/10.1038/s41598-025-87174-6Polyacrylic acidCross-linkIntratracheal instillationPulmonary toxicityFibrosisRat
spellingShingle 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
The degree of cross-linking of polyacrylic acid affects the fibrogenicity in rat lungs
Scientific Reports
Polyacrylic acid
Cross-link
Intratracheal instillation
Pulmonary toxicity
Fibrosis
Rat
title The degree of cross-linking of polyacrylic acid affects the fibrogenicity in rat lungs
title_full The degree of cross-linking of polyacrylic acid affects the fibrogenicity in rat lungs
title_fullStr The degree of cross-linking of polyacrylic acid affects the fibrogenicity in rat lungs
title_full_unstemmed The degree of cross-linking of polyacrylic acid affects the fibrogenicity in rat lungs
title_short The degree of cross-linking of polyacrylic acid affects the fibrogenicity in rat lungs
title_sort degree of cross linking of polyacrylic acid affects the fibrogenicity in rat lungs
topic Polyacrylic acid
Cross-link
Intratracheal instillation
Pulmonary toxicity
Fibrosis
Rat
url https://doi.org/10.1038/s41598-025-87174-6
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