Pulmonary inflammation and cellular responses following exposure to benzalkonium chloride: Potential impact of disrupted pulmonary surfactant homeostasis

• Published in: Toxicology and applied pharmacology Vol. 440; p. 115930
• Main Authors: Park, Eun-Jung, Jin, Seung-Woo, Kang, Min-Sung, Yang, Mi-Jin, Kim, Sung-Hwan, Han, Hyoung-Yun, Kang, Jeong Won
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2022
• Subjects: Animals; Autophagosome; Benzalkonium chloride; Benzalkonium Compounds - toxicity; Disinfectants; Female; Homeostasis; Inflammation; Inhalation; Lamellar body-like structures; Lung; Male; Mice; Pneumonia - chemically induced; Pulmonary Surfactants; Benzalkonium chloride; Inflammation; Disinfectants; Autophagosome; Lamellar body-like structures; Inhalation
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2022.115930

Benzalkonium chloride (BKC) is a prototypical quaternary ammonium disinfectant. Previously, we suggested a no lethal dose level (0.005%) and an LD50 range (0.5–0.05%) of BKC following a single pharyngeal aspiration. Herein, we exposed BKC repeatedly by pharyngeal aspiration for 14 days (0.005 and 0.01%, female mice, total five times with interval of two days, 5 mice/group) and 28 days (0, 0.001, 0.005, and 0.01%, male and female mice, weekly, 16 mice/sex/group). Death following 14 days-repeated exposure did not occur. Meanwhile, chronic pathological lesions were observed in the lung tissues of mice exposed to BKC for 28 days. The total number of bronchial alveolar lavage cells increased, and pulmonary homeostasis of immunologic messenger molecules was disturbed. Following, we investigated BKC-induced cellular responses using human bronchial epithelial cells. The cytotoxicity increased rapidly with concentration. Lysosomal volume, NO production, and lipid peroxidation increased in BKC-treated cells, whereas intracellular ROS level decreased accompanying structural and functional damage of mitochondria. We also found that BKC affected the expression level of immune response, DNA damage, and amino acid biosynthesis-related molecules. More interestingly, lamellar body- and autophagosome-like structures were notably observed in cells exposed to BKC, and necrotic and apoptotic cell death were identified accompanying cell accumulation in the G2/M phase. Therefore, we suggest that repeated respiratory exposure of BKC causes pulmonary inflammation and lung tissue damage and that dead and damaged cells may contribute to the inflammatory response. In addition, the formation process of lamellar body-like structures may function as a key toxicity mechanism. [Display omitted] •28 days-repeated aspiration of BKC induced chronic inflammatory lesions in mice.•Pulmonary exposure of 0.5 μg or less of BKC would be desirable to keep human health.•Dead and dying cells may contribute to BKC-induced inflammatory response.•Lamellar body-like structures formed by BKC exposure may be a type of macroautophagy.•Intracellular accumulation of damaged organelles is a key for BKC-induced toxicity.