Polyhexamethyleneguanidine phosphate induces severe lung inflammation, fibrosis, and thymic atrophy

•The target organs of PHMG-P exposed to lungs were the lungs and the thymus.•PHMG-P induces pulmonary inflammation and fibrosis in a dose-dependent manner.•PHMG-P exposure to the lungs results thymic atrophy and reduction in CD4+/CD8+ cell ratio. Polyhexamethyleneguanidine phosphate (PHMG-P) has bee...

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Veröffentlicht in:Food and chemical toxicology 2014-07, Vol.69, p.267-275
Hauptverfasser: Song, Jeong Ah, Park, Hyun-Ju, Yang, Mi-Jin, Jung, Kyung Jin, Yang, Hyo-Seon, Song, Chang-Woo, Lee, Kyuhong
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Sprache:eng
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Zusammenfassung:•The target organs of PHMG-P exposed to lungs were the lungs and the thymus.•PHMG-P induces pulmonary inflammation and fibrosis in a dose-dependent manner.•PHMG-P exposure to the lungs results thymic atrophy and reduction in CD4+/CD8+ cell ratio. Polyhexamethyleneguanidine phosphate (PHMG-P) has been widely used as a disinfectant because of its strong bactericidal activity and low toxicity. However, in 2011, the Korea Centers for Disease Control and Prevention and the Ministry of Health and Welfare reported that a suspicious outbreak of pulmonary disease might have originated from humidifier disinfectants. The purpose of this study was to assess the toxicity of PHMG-P following direct exposure to the lung. PHMG-P (0.3, 0.9, or 1.5mg/kg) was instilled into the lungs of mice. The levels of proinflammatory markers and fibrotic markers were quantified in lung tissues and flow cytometry was used to evaluate T cell distribution in the thymus. Administration of PHMG-P induced proinflammatory cytokines elevation and infiltration of immune cells into the lungs. Histopathological analysis revealed a dose-dependent exacerbation of both inflammation and pulmonary fibrosis on day 14. PHMG-P also decreased the total cell number and the CD4+/CD8+ cell ratio in the thymus, with the histopathological examination indicating severe reduction of cortex and medulla. The mRNA levels of biomarkers associated with T cell development also decreased markedly. These findings suggest that exposure of lung tissue to PHMG-P leads to pulmonary inflammation and fibrosis as well as thymic atrophy.
ISSN:0278-6915
1873-6351
DOI:10.1016/j.fct.2014.04.027