N-acetyl-L-cysteine protects against inhaled sulfur mustard poisoning in the large swine
N-acetyl-L-cysteine protects against inhaled sulfur mustard poisoning in the large swine
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DOI：
10.3109/15563650.2013.780208
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发表时间：
2013-05-01
影响因子：
3.3
通讯作者：
Sciuto, A. M.
中科院分区：
文献类型：
--
作者：
Jugg, B.;Fairhall, S.;Sciuto, A. M.
上下文硫芥是一种水疱剂，可导致肺部损伤死亡。目前没有有效的治疗方法。N-乙酰-L-半胱氨酸（NAC）具有粘液溶解和抗氧化作用，是细胞谷胱甘肽合成的重要前体。这些行动可能有可能减少芥末引起的肺损伤。Objective.在大型动物模型中评价雾化NAC作为吸入硫芥暴露后治疗的效果。材料和方法。将14只麻醉的手术准备猪暴露于硫芥子气蒸汽（100 mu g.kg（-1），10 min），并在自主呼吸下监测12 h。对照动物没有进一步干预（n = 6）。给药组动物多次吸入剂量的NAC（暴露后+30分钟、2、4、6、8和10小时，1 ml 200mg.ml（-1）Mucomyst（TM），n = 8）。记录心血管和呼吸参数。采集动脉血进行血气分析，同时采集血液和支气管肺泡灌洗液进行血液学和炎症细胞分析。收集尿液以检测硫芥分解产物。取肺组织样品用于组织病理学和实验后分析。结果6只染毒动物中有5只存活至12 h。动脉血氧饱和度（PaO 2）在12 h时显著降低。12 h动脉血二氧化碳分压（PaCO 2）显著升高，动脉血pH和碳酸氢盐（HCO 3-）显著降低。12 h时分流率显著增加。在NAC处理组中，所有动物均存活至12 h（n = 8）。与硫芥对照组相比，动脉血氧饱和度、HCO 3-水平和分流分数显著改善。与硫芥对照组相比，灌洗液中的中性粒细胞和蛋白质浓度显著减少。讨论NAC的粘液溶解和抗氧化特性可能是所看到的有益效果的原因，改善了受硫芥暴露影响的临床相关生理指标。结论吸入硫芥暴露后，雾化NAC的有益效果明显。进一步的治疗益处可由组合疗法方法产生。
Context. Sulfur mustard is a blister agent that can cause death by pulmonary damage. There is currently no effective treatment. N-acetyl-L-cysteine (NAC) has mucolytic and antioxidant actions and is an important pre-cursor of cellular glutathione synthesis. These actions may have potential to reduce mustard-induced lung injury. Objective. Evaluate the effect of nebulised NAC as a post-exposure treatment for inhaled sulfur mustard in a large animal model. Materials and methods. Fourteen anesthetized, surgically prepared pigs were exposed to sulfur mustard vapor (100 mu g.kg(-1), 10 min) and monitored, spontaneously breathing, to 12 h. Control animals had no further intervention (n = 6). Animals in the treatment group were administered multiple inhaled doses of NAC (1 ml of 200 mg.ml(-1) Mucomyst (TM) at + 30 min, 2, 4, 6, 8, and 10 h post-exposure, n = 8). Cardiovascular and respiratory parameters were recorded. Arterial blood was collected for blood gas analysis while blood and bronchoalveolar lavage fluid were collected for hematology and inflammatory cell analysis. Urine was collected to detect a sulfur mustard breakdown product. Lung tissue samples were taken for histopathological and post-experimental analyses. Results. Five of six sulfur mustard-exposed animals survived to 12 h. Arterial blood oxygenation (PaO2) and saturation levels were significantly decreased at 12 h. Arterial blood carbon dioxide (PaCO2) significantly increased, and arterial blood pH and bicarbonate (HCO3-) significantly decreased at 12 h. Shunt fraction was significantly increased at 12 h. In the NAC-treated group all animals survived to 12 h (n = 8). There was significantly improved arterial blood oxygen saturation, HCO3- levels, and shunt fraction compared to those of the sulfur mustard controls. There were significantly fewer neutrophils and lower concentrations of protein in lavage compared to sulfur mustard controls. Discussion. NAC's mucolytic and antioxidant properties may be responsible for the beneficial effects seen, improving clinically relevant physiological indices affected by sulfur mustard exposure. Conclusion. Beneficial effects of nebulized NAC were apparent following inhaled sulfur mustard exposure. Further therapeutic benefit may result from a combination therapy approach.