Ascorbate and deferoxamine administration after chlorine exposure decrease mortality and lung injury in mice.
Ascorbate and deferoxamine administration after chlorine exposure decrease mortality and lung injury in mice.
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DOI：
10.1165/rcmb.2010-0432oc
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发表时间：
2011-08
影响因子：
6.4
通讯作者：
S. Zarogiannis;Asta Jurkuvenaite;S. Fernandez;Stephen F. Doran;A. Yadav;G. Squadrito;E. Postlethwait-
中科院分区：
文献类型：
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作者：
S. Zarogiannis;Asta Jurkuvenaite;S. Fernandez;Stephen F. Doran;A. Yadav;G. Squadrito;E. Postlethwait-
氯（Cl（2））气体暴露造成环境和职业危害，经常导致急性肺损伤。没有有效的治疗方法。我们评估了暴露后给予抗氧化剂对降低C57 BL/6小鼠暴露于600 ppm Cl（2）45分钟并返回室内空气中的死亡率和肺损伤的功效。从暴露后1小时开始，每12小时肌肉注射一次抗坏血酸盐和去铁胺，每24小时鼻吸入一次，持续3天。对照组小鼠暴露于Cl（2）并用溶剂（生理盐水或水）处理。与对照组相比，治疗组的死亡率降低了4倍（22% vs 78%; P = 0.007）。治疗组存活动物的支气管肺泡灌洗液（BAL）中蛋白浓度、细胞计数和上皮细胞显著降低。肺组织抗坏血酸与BAL蛋白以及中性粒细胞和上皮细胞数量呈负相关。此外，与对照组相比，用抗坏血酸和去铁胺处理的小鼠的BAL中脂质过氧化反应降低了三倍。抗坏血酸盐和去铁胺的给药通过减少肺泡毛细血管通透性、炎症、上皮脱落和脂质过氧化降低死亡率并减少肺损伤。
Chlorine (Cl(2)) gas exposure poses an environmental and occupational hazard that frequently results in acute lung injury. There is no effective treatment. We assessed the efficacy of antioxidants, administered after exposure, in decreasing mortality and lung injury in C57BL/6 mice exposed to 600 ppm of Cl(2) for 45 minutes and returned to room air. Ascorbate and deferoxamine were administered intramuscularly every 12 hours and by nose-only inhalation every 24 hours for 3 days starting after 1 hour after exposure. Control mice were exposed to Cl(2) and treated with vehicle (saline or water). Mortality was reduced fourfold in the treatment group compared with the control group (22 versus 78%; P = 0.007). Surviving animals in the treatment group had significantly lower protein concentrations, cell counts, and epithelial cells in their bronchoalveolar lavage (BAL). Lung tissue ascorbate correlated inversely with BAL protein as well as with the number of neutrophils and epithelial cells. In addition, lipid peroxidation was reduced threefold in the BAL of mice treated with ascorbate and deferoxamine when compared with the control group. Administration of ascorbate and deferoxamine reduces mortality and decreases lung injury through reduction of alveolar-capillary permeability, inflammation, and epithelial sloughing and lipid peroxidation.