Liu Lu, Hu Xiaoxuan, Zhang Na, Zhong Yuxu, Zhu Xiao-Ji, Liu Tao
Department of Internal Medicine, Jiaozhou Branch of Shanghai East Hospital, Tongji University, Qingdao, China.
Department of Pulmonary and Critical Care Medicine, Weifang Respiratory Disease Hospital, Weifang, China.
Hum Exp Toxicol. 2024 Jan-Dec;43:9603271241308772. doi: 10.1177/09603271241308772.
Sulfur mustard (SM) is an important chemical warfare agent. The mechanisms underlying SM toxicity have not been completely elucidated. However, oxidative stress and the subsequent damage to macromolecules have been considered ascrucial steps in SM toxicity. In this study, a rat model of SM-induced acute pulmonary injury was established using an equal toxicity dose (1LD). This study employed two methods to directly compare oxidative stress indices in serum enzymes and the epithelial cells of the alveolar septa.
Male Sprague-Dawley rats were randomly divided into intraperitoneal SM, intraperitoneal propylene glycol control, tracheal SM, tracheal propylene glycol control, and control groups. SM-induced serum enzyme levels and protein expression in the epithelial cells of the alveolar septa were measured using enzyme-linked immunosorbent assay and immunohistochemistry.
Serum levels of superoxide dismutase, catalase, and glutathione peroxidase were upregulated in the intraperitoneal SM group compared with those in the tracheal SM group. Positive expression ratios of CuZn-superoxide dismutase, Mn-superoxide dismutase, paraoxonase-1, and apolipoprotein-1 proteins in the epithelial cells of the alveolar septa in the intraperitoneal SM group were elevated compared with those in the tracheal SM group.
Under SM (1LD) exposure, there were significantly higher serum enzyme levels and protein expressions in the epithelial cells of the alveolar septa of rats injected with SM intraperitoneally compared with SM administered by intratracheal instillation. The results demonstrated that the differences in oxidative stress indices at the molecular level in SM-induced pulmonary injury were dependent on the route of exposure.
硫芥是一种重要的化学战剂。硫芥毒性的潜在机制尚未完全阐明。然而，氧化应激及随后对大分子的损伤被认为是硫芥毒性中的关键步骤。在本研究中，使用等毒性剂量（1LD）建立了硫芥诱导的大鼠急性肺损伤模型。本研究采用两种方法直接比较血清酶和肺泡隔上皮细胞中的氧化应激指标。
将雄性Sprague-Dawley大鼠随机分为腹腔注射硫芥组、腹腔注射丙二醇对照组、气管内注射硫芥组、气管内注射丙二醇对照组和对照组。采用酶联免疫吸附测定法和免疫组织化学法检测硫芥诱导的血清酶水平及肺泡隔上皮细胞中的蛋白表达。
与气管内注射硫芥组相比，腹腔注射硫芥组血清中超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶水平上调。与气管内注射硫芥组相比，腹腔注射硫芥组肺泡隔上皮细胞中铜锌超氧化物歧化酶、锰超氧化物歧化酶、对氧磷酶-1和载脂蛋白-1蛋白的阳性表达率升高。
在硫芥（1LD）暴露下，与气管内滴注硫芥相比，腹腔注射硫芥的大鼠肺泡隔上皮细胞中的血清酶水平和蛋白表达显著更高。结果表明，硫芥诱导的肺损伤在分子水平上氧化应激指标的差异取决于暴露途径。
