Allon Nahum, Amir Adina, Manisterski Eliau, Rabinovitz Ishay, Dachir Shlomit, Kadar Tamar
Department of Pharmacology, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona 74100, Israel.
Toxicol Appl Pharmacol. 2009 Dec 1;241(2):154-62. doi: 10.1016/j.taap.2009.08.006. Epub 2009 Aug 12.
Guinea pigs (GP) were exposed (head only) in individual plethysmographs to various concentrations of sulfur mustard vapor, determined online, using FTIR attached to flow chamber. The LCt(50) and the inhaled LD(50) were calculated at different time points post exposure. Surviving animals were monitored for clinical symptoms, respiratory parameters and body weight changes for up to 30 days. Clinical symptoms were noted at 3 h post exposure, characterized by erythematic and swelling nose with extensive mucous secretion (with or without bleeding). At 6 h post exposure most of the guinea pigs had breathing difficulties, rhonchi and dyspnea and few deaths were noted. These symptoms peaked at 48 h and were noted up to 8 days, associated with few additional deaths. Thereafter, a spontaneous healing was noted, characterized by recovery of respiratory parameters and normal weight gain with almost complete apparent healing within 2 weeks. Histopathological evaluation of lungs and trachea in the surviving GPs at 4 weeks post exposure revealed a dose-dependent residual injury in both lung and trachea expressed by abnormal recovery of the tracheal epithelium concomitant with a dose-dependent increase in cellular volume in the lungs. These abnormal epithelial regeneration and lung remodeling were accompanied with significant changes in protein, LDH, differential cell count and glutathione levels in the bronchoalveolar lavage (BAL). It is suggested that the abnormal epithelial growth and cellular infiltration into the lung as well as the continuous lung inflammation could cause recurrent lung injury similar to that reported for HD exposed human casualties.
将豚鼠（GP）（仅头部）置于个体体积描记器中，暴露于通过连接流动腔室的傅里叶变换红外光谱仪在线测定的不同浓度的硫芥蒸气中。在暴露后的不同时间点计算LCt(50)和吸入性LD(50)。对存活的动物监测临床症状、呼吸参数和体重变化，长达30天。在暴露后3小时记录临床症状，其特征为鼻子红斑和肿胀，伴有大量粘液分泌（有或无出血）。在暴露后6小时，大多数豚鼠出现呼吸困难、干啰音和呼吸急促，并记录到少数死亡。这些症状在48小时达到峰值，并持续到8天，伴有少数额外死亡。此后，观察到自发愈合，其特征为呼吸参数恢复和体重正常增加，在2周内几乎完全明显愈合。对暴露后4周存活的豚鼠的肺和气管进行组织病理学评估，结果显示肺和气管均存在剂量依赖性残留损伤，表现为气管上皮异常修复，同时肺细胞体积呈剂量依赖性增加。这些异常的上皮再生和肺重塑伴随着支气管肺泡灌洗（BAL）中蛋白质、乳酸脱氢酶、细胞分类计数和谷胱甘肽水平的显著变化。有人提出，异常的上皮生长和细胞浸润到肺中以及持续的肺部炎症可能导致与暴露于HD的人类伤亡所报道的类似的复发性肺损伤。
