Didecyldimethylammonium chloride induces pulmonary inflammation and fibrosis in mice.
Didecyldimethylammonium chloride (DDAC) is used worldwide as a germicide, in antiseptics, and as a wood preservative, and can cause adverse pulmonary disease in humans. However, the pulmonary toxicity of DDAC has not yet been thoroughly investigated. Mice were intratracheally instilled with DDAC to the lung and the bronchoalveolar lavage (BAL) fluid and lung tissues were collected to assess dose- and time-related pulmonary injury. Exposure to 1500 μg/kg of DDAC caused severe morbidity with pulmonary congestive oedema. When the BAL fluid from survivors was examined on day 3 after treatment, exposure to 150 μg/kg of DDAC caused weakly induced inflammation, and exposure to 15μg/kg did not cause any visible effects. Next, we observed pulmonary changes that occurred up to day 20 after 150 μg/kg of DDAC exposure. Pulmonary inflammation peaked on day 7 and was confirmed by expression of interleukin-6, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, and regulated upon activation, normal T-cell expressed and secreted in the BAL fluid; these changes were accompanied by altered gene expression of their chemokine (C-C motif) receptor (Ccr) 1, Ccr2, Ccr3, and Ccr5. Cytotoxicity evoked by DDAC was related to the inflammatory changes and was confirmed by an in vitro study using isolated mouse lung fibroblasts. The inflammatory phase was accompanied or followed by pulmonary remodeling, i.e., fibrosis, which was evident in the mRNA expression of type I procollagen. These results suggest that administering DDAC by intratracheal instillation causes pulmonary injury in mice, and occupational exposure to DDAC might be a potential hazard to human health.
Ohnuma
Aya
A
Laboratory of Pathology, Toxicology Division, Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso, Ibaraki, Japan.
Yoshida
Toshinori
T
Tajima
Haruka
H
Fukuyama
Tomoki
T
Hayashi
Koichi
K
Yamaguchi
Satoru
S
Ohtsuka
Ryoichi
R
Sasaki
Junya
J
Fukumori
Junko
J
Tomita
Mariko
M
Kojima
Sayuri
S
Takahashi
Naofumi
N
Takeuchi
Yukiko
Y
Kuwahara
Maki
M
Takeda
Makio
M
Kosaka
Tadashi
T
Nakashima
Nobuaki
N
Harada
Takanori
T
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000139:chemically induced*; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D000644:Quaternary Ammonium Compounds / Q000633:toxicity*; D019707:Receptors, Chemokine / Q000235:genetics
D024042:Collagen Type I; D000644:Quaternary Ammonium Compounds; D019707:Receptors, Chemokine; C027118:didecyldimethylammonium