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Polyhexamethyleneguanidine phosphate induces severe lung inflammation,fibrosis, and thymic atrophy
Affiliation:1. Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, Leontovich Str.,9, 01030 Kyiv, Ukraine;2. Department of Muscle Biochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, Leontovich Str., 9, 01030 Kyiv, Ukraine;3. Department of Cell Signalling, Palladin Institute of Biochemistry, NAS of Ukraine, Leontovich Str.,9, 01030 Kyiv, Ukraine;4. Department of Ecology, Rivne State University of Humanities, Plastova Str., 29a, 33028 Rivne, Ukraine;1. Department of Environmental Health, Korea National Open University, Seoul, South Korea;2. Asian Citizen''s Center for Environment and Health, Seoul, South Korea;3. School of Public Health, Seoul National University, Seoul, South Korea;4. Department of Pediatrics, Chonnam National University Hospital, Gwangju, South Korea;5. Department of Pulmonary and Critical Care Medicine, Asan Medical Center, Univ. of Ulsan College of Medicine, Seoul, South Korea;6. Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea;7. Department of Occupational and Environmental Medicine, Gachon University Gil Medical Center, Incheon, South Korea;8. Department of Occupational and Environmental Health, Graduate School of Public Health, Yonsei University, Seoul, South Korea;9. Department of Preventive Medicine, Yonsei University, College of Medicine, Seoul, South Korea;10. Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Abstract: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 1.5 mg/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.
Keywords:Polyhexamethyleneguanidine phosphate  Humidifier disinfectant  Pulmonary inflammation  Lung fibrosis
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