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

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.
AuthorsJeong Ah Song, Hyun-Ju Park, Mi-Jin Yang, Kyung Jin Jung, Hyo-Seon Yang, Chang-Woo Song, Kyuhong Lee
JournalFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 69 Pg. 267-75 (Jul 2014) ISSN: 1873-6351 [Electronic] England
PMID24769016 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Ltd. All rights reserved.
Chemical References
  • Cytokines
  • Guanidines
  • polyhexamethyleneguanidine
Topics
  • Animals
  • Atrophy (chemically induced)
  • Body Weight (drug effects)
  • CD4-Positive T-Lymphocytes (drug effects)
  • CD8-Positive T-Lymphocytes (drug effects)
  • Cytokines (metabolism)
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation (drug effects)
  • Guanidines (toxicity)
  • Male
  • Mice, Inbred C57BL
  • Organ Size (drug effects)
  • Pneumonia (chemically induced, pathology)
  • Pulmonary Fibrosis (chemically induced, pathology)
  • Thymus Gland (drug effects, pathology)

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