Related Experiment Video
Updated: Apr 19, 2026
Visualizing Lung Cellular Adaptations during Combined Ozone and LPS Induced Murine Acute Lung Injury
Published on: March 21, 2021
Mechanism underlying acute lung injury due to sulfur mustard exposure in rats
Zhu Xiaoji1, Meng Xiao2, Xu Rui2
1Department of Respiration, The 89th Hospital of PLA, Weifang, China.
Abstract:
Sulfur mustard (SM), a bifunctional alkylating agent that causes severe lung damage, is a significant threat to both military and civilian populations. The mechanisms mediating the cytotoxic effects of SM are unknown and were investigated in this study. The purpose of this study was to establish a rat model of SM-induced lung injury to observe the resulting changes in the lungs. Male rats (Sprague Dawley) were anesthetized, intratracheally intubated, and exposed to 2 mg/kg of SM by intratracheal instillation. Animals were euthanized 6, 24, 48, and 72 h post-exposure, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. Exposure of rats to SM resulted in rapid pulmonary toxicity, including partial bronchiolar epithelium cell shedding, focal ulceration, and an increased amount of inflammatory exudate and number of cells in the alveoli. There was also evidence that the protein content and cell count of BALF peaked at 48 h, and the alveolar septum was widened and filled with lymphocytes. SM exposure also resulted in partial loss of type I alveolar epithelial cell membranes, fuzzy mitochondrial cristae, detachment and dissociation of ribosomes attached to the surface of rough endoplasmic reticulum, cracked, missing, and disorganized microvilli of type II alveolar epithelial cells, and increased apoptotic cells in the alveolar septum. The propylene glycol control group, however, was the same as the normal group. These data demonstrate that the mechanism of a high concentration of SM (2 mg/kg) induced acute lung injury include histologic changes, inflammatory reactions, apoptosis, oxidative stress, and nuclear DNA damage; the degree of injury is time dependent.
Insights
Sulfur mustard (SM) causes severe lung injury through mechanisms including inflammation, apoptosis, and DNA damage. This study established a rat model to observe these time-dependent cytotoxic effects.
Area of Science:
- Toxicology
- Pulmonary Medicine
- Cell Biology
Background:
- Sulfur mustard (SM) is a bifunctional alkylating agent causing severe lung damage.
- The cytotoxic mechanisms of SM-induced lung injury remain largely unknown.
- Understanding these mechanisms is crucial for developing effective countermeasures.
Purpose of the Study:
- To establish a rat model of SM-induced acute lung injury.
- To investigate the time-dependent cellular and histological changes following SM exposure.
- To elucidate the mechanisms underlying SM-induced pulmonary toxicity.
Main Methods:
- Male Sprague Dawley rats were exposed to 2 mg/kg of SM via intratracheal instillation.
- Bronchoalveolar lavage fluid (BALF) and lung tissues were collected at 6, 24, 48, and 72 hours post-exposure.
- Histological examination and cellular analysis of BALF and lung tissues were performed.
Main Results:
- SM exposure led to rapid pulmonary toxicity, including epithelial cell shedding, ulceration, and inflammatory cell infiltration.
- BALF protein content and cell count peaked at 48 hours post-exposure.
- Ultrastructural changes included mitochondrial damage, endoplasmic reticulum dysfunction, and microvilli alterations in alveolar epithelial cells.
- Increased apoptosis and nuclear DNA damage were observed in the alveolar septum, indicating oxidative stress.
Conclusions:
- SM induces acute lung injury through a complex interplay of histological damage, inflammatory responses, apoptosis, oxidative stress, and DNA damage.
- The observed lung injury is time-dependent, with significant changes occurring within 72 hours post-exposure.
- The established rat model provides valuable insights into the pathogenesis of SM-induced lung injury, aiding in the development of therapeutic strategies.
