TY - JOUR
T1 - Formation of lamellar body-like structure may be an initiator of didecyldimethylammonium chloride-induced toxic response
AU - Park, Eun Jung
AU - Seong, Eunsol
AU - Kang, Min Sung
AU - Lee, Gwang Hee
AU - Kim, Dong Wan
AU - Han, Ji Seok
AU - Lim, Hyun Ji
AU - Lee, Seung Hyeun
AU - Han, Hyoung Yun
N1 - Funding Information:
This work was supported by a grant from Kyung Hee University in 2018 (20180872 and 20182222) and the Ministry of Science and ICT (NRF-2015M3A7B6027948 and NRF-2016M3A9C4953144).
Funding Information:
This work was supported by a grant from Kyung Hee University in 2018 ( 20180872 and 20182222 ) and the Ministry of Science and ICT ( NRF-2015M3A7B6027948 and NRF-2016M3A9C4953144 ).
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Due to the pandemic of coronavirus disease 2019, the use of disinfectants is rapidly increasing worldwide. Didecyldimethylammonium chloride (DDAC) is an EPA-registered disinfectant, it was also a component in humidifier disinfectants that had caused idiopathic pulmonary diseases in Korea. In this study, we identified the possible pulmonary toxic response and mechanism using human bronchial epithelial (BEAS-2B) cells and mice. First, cell viability decreased sharply at a 4 μg/mL of concentration. The volume of intracellular organelles and the ROS level reduced, leading to the formation of apoptotic bodies and an increase of the LDH release. Secretion of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and matrix metalloproteinase-1 also significantly increased. More importantly, lamellar body-like structures were formed in both the cells and mice exposed to DDAC, and the expression of both the indicator proteins for lamellar body (ABCA3 and Rab11a) and surfactant proteins (A, B, and D) was clearly enhanced. In addition, chronic fibrotic pulmonary lesions were notably observed in mice instilled twice (weekly) with DDAC (500 μg), ultimately resulting in death. Taken together, we suggest that disruption of pulmonary surfactant homeostasis may contribute to DDAC-induced cell death and subsequent pathophysiology and that the formation of lamellar body-like structures may play a role as the trigger. In addition, we propose that the cause of sudden death of mice exposed to DDAC should be clearly elucidated for the safe application of DDAC.
AB - Due to the pandemic of coronavirus disease 2019, the use of disinfectants is rapidly increasing worldwide. Didecyldimethylammonium chloride (DDAC) is an EPA-registered disinfectant, it was also a component in humidifier disinfectants that had caused idiopathic pulmonary diseases in Korea. In this study, we identified the possible pulmonary toxic response and mechanism using human bronchial epithelial (BEAS-2B) cells and mice. First, cell viability decreased sharply at a 4 μg/mL of concentration. The volume of intracellular organelles and the ROS level reduced, leading to the formation of apoptotic bodies and an increase of the LDH release. Secretion of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and matrix metalloproteinase-1 also significantly increased. More importantly, lamellar body-like structures were formed in both the cells and mice exposed to DDAC, and the expression of both the indicator proteins for lamellar body (ABCA3 and Rab11a) and surfactant proteins (A, B, and D) was clearly enhanced. In addition, chronic fibrotic pulmonary lesions were notably observed in mice instilled twice (weekly) with DDAC (500 μg), ultimately resulting in death. Taken together, we suggest that disruption of pulmonary surfactant homeostasis may contribute to DDAC-induced cell death and subsequent pathophysiology and that the formation of lamellar body-like structures may play a role as the trigger. In addition, we propose that the cause of sudden death of mice exposed to DDAC should be clearly elucidated for the safe application of DDAC.
KW - Didecyldimethylammonium chloride
KW - Disinfectants
KW - Idiopathic pulmonary fibrosis
KW - Lamella body
KW - Matrix metalloproteinase-1
KW - Quaternary ammonium compounds
UR - http://www.scopus.com/inward/record.url?scp=85089522183&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2020.115182
DO - 10.1016/j.taap.2020.115182
M3 - Article
C2 - 32763356
AN - SCOPUS:85089522183
VL - 404
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
M1 - 115182
ER -