Alterations in Apoptotic Cell Populations, Protein Markers, and Gene Expression Patterns in Rats with Sulfur Mustard-induced Pulmonary Injuries

Tao  Liu; Na  Zhang; Xin  Shu; Xiaoxuan  Hu; Jingtong  Li; Yuxu  Zhong; Jinyuan  Tang; Xiao-ji  Zhu

doi:10.18502/ijaai.v25i2.20803

Tao Liu Department of Respiration, The 80th Group Army Hospital of People’s Liberation Army, Weifang, China
Na Zhang Department of Respiration, The 80th Group Army Hospital of People’s Liberation Army, Weifang, China
Xin Shu Department of Dermatology, The Third Medical Center of Chinese PLA General Hospital, Beijing, China
Xiaoxuan Hu Department of Pulmonary and Critical Care Medicine, Weifang No. 2 People’s Hospital, Weifang, China
Jingtong Li Department of Respiration, The 80th Group Army Hospital of People’s Liberation Army, Weifang, China
Yuxu Zhong Institute of Toxicology and Pharmacology, Academy of Military Medical Sciences, Beijing, China
Jinyuan Tang Department of Respiration, The 80th Group Army Hospital of People’s Liberation Army, Weifang, China
Xiao-ji Zhu Department of Respiration, The 80th Group Army Hospital of People’s Liberation Army, Weifang, China

DOI: https://doi.org/10.18502/ijaai.v25i2.20803

Keywords: Acute pulmonary injury; Apoptosis; Equal lethal dose; Sulfur mustard

Abstract

Sulfur mustard (SM) is a potent chemical warfare agent that causes severe cutaneous, ocular, and pulmonary injuries, with respiratory tract damage being the most life-threatening. Despite its well-documented toxicity, the cellular mechanisms driving SM-induced apoptosis remain poorly understood. This study seeks to elucidate the apoptotic pathways involved in SM-induced pulmonary injury using a rat model.

We induced acute lung injury through two delivery methods: intraperitoneal injection (8 mg/kg) and intratracheal instillation (2 mg/kg) of SM, with both doses representing 1 LD₅₀. We assessed apoptosis-related proteins and gene expression through TUNEL staining, immunohistochemistry, and quantitative real-time PCR analyses.

Intraperitoneal administration of SM resulted in significantly elevated expression of apoptotic markers including annexin A1, annexin A2, cytochrome C, caspase-12, and JNK3, in alveolar epithelial cells compared to intratracheal delivery. Both TUNEL assays and immunohistochemical staining confirmed these findings. These results indicate that intraperitoneal SM exposure triggers more severe apoptotic responses in alveolar epithelial cells than intratracheal exposure at equivalent doses.

These findings demonstrate that intraperitoneal models can effectively identify apoptosis-related molecular targets suitable for therapeutic development.