Related Experiment Video
Updated: Jun 4, 2025
The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat
Published on: June 17, 2016
Didecyldimethylammonium chloride-induced lung fibrosis may be associated with phospholipidosis
Wonkyun Jung1, Mi-Jin Yang2, Min-Sung Kang2
1College of Medicine, Graduate School, Kyung Hee University, 02447, Republic of Korea.
Abstract:
In the current study, we dosed didecyldimethylammonium chloride (DDAC) in mice by pharyngeal aspiration for 28 days or 90 days (weekly) and tried to elucidate the relationship between lamellar body formation and the lesions. When exposed for 28 days (0, 5, 10, 50, and 100 μg/head), all the mice in the 50 and 100 μg/head groups died since Day 2 after the third dosing (Day 16 after the first dosing). Edema, necrosis of bronchiolar and alveolar epithelium, and fibrinous exudate were observed in the lungs of all the dead mice, and chronic inflammatory lesions were observed in the lung tissues of alive mice. When dosed with DDAC of 0, 1, 4, and 8 μg/head for 13 weeks, the total number of pulmonary cells and the pulmonary levels of pro- and anti-inflammatory cytokines significantly increased, and chronic inflammatory lesions were detected with the production of collagen, collagen fibers, and lamellar body-like structures. Swelling of the nuclear envelope and nucleoplasmic components and generation of lipid droplets were also notably observed in the lung tissues of DDAC (8 μg/head)-treated mice. Furthermore, transcriptomic analysis performed using human bronchial epithelial cells showed that DDAC affected the expression of DNA damage, ER stress, lipid metabolism, and transcription regulation-related genes at 6 h after treatment, as it did 24 h treatment and that early growth response factor 1 gene was added to a list of the most up-regulated genes. Meanwhile, cytokines that are associated with the pathology of chronic lung diseases (IL-11, IL-24, and TGF-β) were slightly increased in the lung of DDAC-treated mice, and only the pulmonary level of CCL-2, but not CXCL-1 and CCL-3, increased in both sexes of mice. More importantly, the GM-CSF level increased dose-dependently in the lungs of both sexes of mice exposed to DDAC. Considering that the wound-healing process can take several weeks to complete, we suggest that DDAC-induced pulmonary fibrosis may be attributable to disruption of the wound-healing process due to continuous exposure to DDAC. We also hypothesize that the formation of lamellar bodies may be attributable to lysosomal accumulation of phospholipids separated from the destroyed lung tissue membrane.
Insights
Didecyldimethylammonium chloride (DDAC) exposure in mice caused lung inflammation, cell damage, and fibrosis, potentially by disrupting wound healing. Lamellar body formation may result from lysosomal accumulation of damaged lung tissue components.
Area of Science:
- Toxicology
- Pulmonary Medicine
- Cell Biology
Background:
- Didecyldimethylammonium chloride (DDAC) is a quaternary ammonium compound with antimicrobial properties.
- Understanding the pulmonary toxicity of DDAC is crucial due to its widespread use and potential for inhalation exposure.
- Previous studies have indicated potential respiratory effects, but the mechanisms and long-term consequences require further investigation.
Purpose of the Study:
- To investigate the relationship between lamellar body formation and lung lesions induced by DDAC exposure in mice.
- To elucidate the molecular mechanisms underlying DDAC-induced pulmonary toxicity and fibrosis.
- To assess the dose-dependent effects and temporal dynamics of DDAC exposure on lung tissue and cellular responses.
Main Methods:
- Mice were exposed to DDAC via pharyngeal aspiration for 28 days or 90 days (weekly) at various doses.
- Histopathological examination of lung tissues was performed to identify lesions, inflammation, necrosis, and collagen deposition.
- Pulmonary cell counts, cytokine levels (pro- and anti-inflammatory), and gene expression (transcriptomic analysis) were analyzed.
- Specific attention was given to the formation of lamellar bodies and changes in nuclear envelope and lipid droplets.
Main Results:
- Acute DDAC exposure (28 days) led to high mortality at higher doses (50 and 100 μg/head) with observed edema, necrosis, and inflammation.
- Subchronic DDAC exposure (90 days) resulted in increased pulmonary cells, elevated pro- and anti-inflammatory cytokines, collagen production, and lamellar body-like structures.
- Transcriptomic analysis revealed DDAC's impact on DNA damage, ER stress, lipid metabolism, and transcription regulation, with early growth response factor 1 (EGR1) being upregulated.
- Dose-dependent increases in granulocyte-macrophage colony-stimulating factor (GM-CSF) were observed, alongside slight increases in IL-11, IL-24, TGF-β, and CCL-2.
Conclusions:
- Continuous DDAC exposure can induce pulmonary fibrosis, likely by disrupting the natural wound-healing process.
- The formation of lamellar bodies is hypothesized to be a consequence of lysosomal accumulation of phospholipids from damaged lung membranes.
- DDAC exposure triggers significant inflammatory and cellular responses in the lungs, highlighting its potential as a respiratory toxicant.
More Related Videos
06:29Adoptive Transfer of IL-33-Stimulated Macrophages into Bleomycin-Induced Mouse Models to Study Their Effect on Idiopathic Pulmonary Fibrosis In Vivo
Published on: May 5, 2023
07:11Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis
Published on: May 23, 2025
Related Concept Videos
01:27Synthesis of Phosphatidylcholine in the ER Membrane
The major components of all eukaryotic cell...
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
Chronic Inflammation