Mechanisms of pulmonary disease in F344 rats after workplace-relevant inhalation exposure to cross-linked water-soluble acrylic acid polymers
Abstract Background Recently in Japan, six workers at a chemical plant that manufactures resins developed interstitial lung diseases after being involved in loading and packing cross-linked water-soluble acrylic acid polymers (CWAAPs). The present study focused on assessing lung damage in rats cause...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12931-023-02355-z |
| _version_ | 1827983053441466368 |
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| author | Shotaro Yamano Tomoki Takeda Yuko Goto Shigeyuki Hirai Yusuke Furukawa Yoshinori Kikuchi Kyohei Misumi Masaaki Suzuki Kenji Takanobu Hideki Senoh Misae Saito Hitomi Kondo Yoichiro Kobashi Kenzo Okamoto Takumi Kishimoto Yumi Umeda |
| author_facet | Shotaro Yamano Tomoki Takeda Yuko Goto Shigeyuki Hirai Yusuke Furukawa Yoshinori Kikuchi Kyohei Misumi Masaaki Suzuki Kenji Takanobu Hideki Senoh Misae Saito Hitomi Kondo Yoichiro Kobashi Kenzo Okamoto Takumi Kishimoto Yumi Umeda |
| author_sort | Shotaro Yamano |
| collection | DOAJ |
| description | Abstract Background Recently in Japan, six workers at a chemical plant that manufactures resins developed interstitial lung diseases after being involved in loading and packing cross-linked water-soluble acrylic acid polymers (CWAAPs). The present study focused on assessing lung damage in rats caused by workplace-relevant inhalation exposure to CWAAP and investigated the molecular and cellular mechanisms involved in lung lesion development. Methods Using a whole-body inhalation exposure system, male F344 rats were exposed once to 40 or 100 mg/m3 of CWAAP-A for 4 h or to 15 or 40 mg/m3 of CWAAP-A for 4 h per day once per week for 2 months (9 exposures). In a separate set of experiments, male F344 rats were administered 1 mg/kg CWAAP-A or CWAAP-B by intratracheal instillation once every 2 weeks for 2 months (5 doses). Lung tissues, mediastinal lymph nodes, and bronchoalveolar lavage fluid were collected and subjected to biological and histopathological analyses. Results A single 4-h exposure to CWAAP-A caused alveolar injury, and repeated exposures resulted in regenerative changes in the alveolar epithelium with activation of TGFβ signaling. During the recovery period after the last exposure, some alveolar lesions were partially healed, but other lesions developed into alveolitis with fibrous thickening of the alveolar septum. Rats administered CWAAP-A by intratracheal instillation developed qualitatively similar pulmonary pathology as rats exposed to CWAAP-A by inhalation. At 2 weeks after intratracheal instillation, rats administered CWAAP-B appeared to have a slightly higher degree of lung lesions compared to rats administered CWAAP-A, however, there was no difference in pulmonary lesions in the CWAAP-A and CWAAP-B exposed rats examined 18 weeks after administration of these materials. Conclusions The present study reports our findings on the cellular and molecular mechanisms of pulmonary disease in rats after workplace-relevant inhalation exposure to CWAAP-A. This study also demonstrates that the lung pathogenesis of rats exposed to CWAAP-A by systemic inhalation was qualitatively similar to that of rats administered CWAAP-A by intratracheal instillation. Graphical Abstract |
| first_indexed | 2024-04-09T22:41:36Z |
| format | Article |
| id | doaj.art-7375b04912f347cf991c1be9cd2aa773 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-04-09T22:41:36Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-7375b04912f347cf991c1be9cd2aa7732023-03-22T12:07:51ZengBMCRespiratory Research1465-993X2023-02-0124112610.1186/s12931-023-02355-zMechanisms of pulmonary disease in F344 rats after workplace-relevant inhalation exposure to cross-linked water-soluble acrylic acid polymersShotaro Yamano0Tomoki Takeda1Yuko Goto2Shigeyuki Hirai3Yusuke Furukawa4Yoshinori Kikuchi5Kyohei Misumi6Masaaki Suzuki7Kenji Takanobu8Hideki Senoh9Misae Saito10Hitomi Kondo11Yoichiro Kobashi12Kenzo Okamoto13Takumi Kishimoto14Yumi Umeda15Japan Bioassay Research Center, Japan Organization of Occupational Health and SafetyJapan Bioassay Research Center, Japan Organization of Occupational Health and SafetyJapan Bioassay Research Center, Japan Organization of Occupational Health and SafetyJapan Bioassay Research Center, Japan Organization of Occupational Health and SafetyJapan Bioassay Research Center, Japan Organization of Occupational Health and SafetyJapan Bioassay Research Center, Japan Organization of Occupational Health and SafetyJapan Bioassay Research Center, Japan Organization of Occupational Health and SafetyJapan Bioassay Research Center, Japan Organization of Occupational Health and SafetyJapan Bioassay Research Center, Japan Organization of Occupational Health and SafetyJapan Bioassay Research Center, Japan Organization of Occupational Health and SafetyJapan Bioassay Research Center, Japan Organization of Occupational Health and SafetyJapan Bioassay Research Center, Japan Organization of Occupational Health and SafetyDepartment of Pathology, Tenri HospitalDepartment of Pathology, Hokkaido Chuo Rosai Hospital, Japan Organization of Occupational Health and SafetyDirector of Research and Training Center for Asbestos-Related DiseasesJapan Bioassay Research Center, Japan Organization of Occupational Health and SafetyAbstract Background Recently in Japan, six workers at a chemical plant that manufactures resins developed interstitial lung diseases after being involved in loading and packing cross-linked water-soluble acrylic acid polymers (CWAAPs). The present study focused on assessing lung damage in rats caused by workplace-relevant inhalation exposure to CWAAP and investigated the molecular and cellular mechanisms involved in lung lesion development. Methods Using a whole-body inhalation exposure system, male F344 rats were exposed once to 40 or 100 mg/m3 of CWAAP-A for 4 h or to 15 or 40 mg/m3 of CWAAP-A for 4 h per day once per week for 2 months (9 exposures). In a separate set of experiments, male F344 rats were administered 1 mg/kg CWAAP-A or CWAAP-B by intratracheal instillation once every 2 weeks for 2 months (5 doses). Lung tissues, mediastinal lymph nodes, and bronchoalveolar lavage fluid were collected and subjected to biological and histopathological analyses. Results A single 4-h exposure to CWAAP-A caused alveolar injury, and repeated exposures resulted in regenerative changes in the alveolar epithelium with activation of TGFβ signaling. During the recovery period after the last exposure, some alveolar lesions were partially healed, but other lesions developed into alveolitis with fibrous thickening of the alveolar septum. Rats administered CWAAP-A by intratracheal instillation developed qualitatively similar pulmonary pathology as rats exposed to CWAAP-A by inhalation. At 2 weeks after intratracheal instillation, rats administered CWAAP-B appeared to have a slightly higher degree of lung lesions compared to rats administered CWAAP-A, however, there was no difference in pulmonary lesions in the CWAAP-A and CWAAP-B exposed rats examined 18 weeks after administration of these materials. Conclusions The present study reports our findings on the cellular and molecular mechanisms of pulmonary disease in rats after workplace-relevant inhalation exposure to CWAAP-A. This study also demonstrates that the lung pathogenesis of rats exposed to CWAAP-A by systemic inhalation was qualitatively similar to that of rats administered CWAAP-A by intratracheal instillation. Graphical Abstracthttps://doi.org/10.1186/s12931-023-02355-zCross-linked water-soluble acrylic acid polymer (CWAAP)Workplace-relevant inhalation exposureIntratracheal instillationRatTransforming growth factorPulmonary disease |
| spellingShingle | Shotaro Yamano Tomoki Takeda Yuko Goto Shigeyuki Hirai Yusuke Furukawa Yoshinori Kikuchi Kyohei Misumi Masaaki Suzuki Kenji Takanobu Hideki Senoh Misae Saito Hitomi Kondo Yoichiro Kobashi Kenzo Okamoto Takumi Kishimoto Yumi Umeda Mechanisms of pulmonary disease in F344 rats after workplace-relevant inhalation exposure to cross-linked water-soluble acrylic acid polymers Respiratory Research Cross-linked water-soluble acrylic acid polymer (CWAAP) Workplace-relevant inhalation exposure Intratracheal instillation Rat Transforming growth factor Pulmonary disease |
| title | Mechanisms of pulmonary disease in F344 rats after workplace-relevant inhalation exposure to cross-linked water-soluble acrylic acid polymers |
| title_full | Mechanisms of pulmonary disease in F344 rats after workplace-relevant inhalation exposure to cross-linked water-soluble acrylic acid polymers |
| title_fullStr | Mechanisms of pulmonary disease in F344 rats after workplace-relevant inhalation exposure to cross-linked water-soluble acrylic acid polymers |
| title_full_unstemmed | Mechanisms of pulmonary disease in F344 rats after workplace-relevant inhalation exposure to cross-linked water-soluble acrylic acid polymers |
| title_short | Mechanisms of pulmonary disease in F344 rats after workplace-relevant inhalation exposure to cross-linked water-soluble acrylic acid polymers |
| title_sort | mechanisms of pulmonary disease in f344 rats after workplace relevant inhalation exposure to cross linked water soluble acrylic acid polymers |
| topic | Cross-linked water-soluble acrylic acid polymer (CWAAP) Workplace-relevant inhalation exposure Intratracheal instillation Rat Transforming growth factor Pulmonary disease |
| url | https://doi.org/10.1186/s12931-023-02355-z |
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