High-level concentrations of chlorine (Cl2) can cause life-threatening lung injuries and the objective in this study was to understand the pathogenesis of short-term sequelae of Cl2-induced lung injury and to evaluate whether pre-treatment with the antioxidant N-acetyl cysteine (NAC) could counteract these injuries using Cl2-exposed precision-cut lung slices (PCLS). The lungs of Sprague-Dawley rats were filled with agarose solution and cut into 250 µm-thick slices that were exposed to Cl2 (20-600 ppm) and incubated for 30 min. The tissue slices were pre-treated with NAC (5-25 mM) before exposure to Cl2. Toxicological responses were analyzed after 5 h by measurement of LDH, WST-1 and inflammatory mediators (IL-1β, IL-6 and CINC-1) in medium or lung tissue homogenate. Exposure to Cl2 induced a concentration-dependent cytotoxicity (LDH/WST-1) and IL-1β release in medium. Similar cytokine response was detected in tissue homogenate. Contraction of larger airways was measured using electric-field-stimulation method, 200 ppm and control slices had similar contraction level (39 ± 5%) but in the 400 ppm Cl2 group, the evoked contraction was smaller (7 ± 3%) possibly due to tissue damage. NAC-treatment improved cell viability and reduced tissue damage and the contraction was similar to control levels (50 ± 11%) in the NAC treated Cl2-exposed slices. In conclusion, Cl2 induced a concentration-dependent lung tissue damage that was effectively prevented with pre-treatment with NAC. There is a great need to improve the medical treatment of acute lung injury and this PCLS method offers a way to identify and to test new concepts of treatment of Cl2-induced lung injuries.

中文翻译：

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N-乙酰半胱氨酸在体外模型中防止氯诱导的组织损伤

高浓度的氯 (Cl2) 会导致危及生命的肺损伤，本研究的目的是了解 Cl2 诱导的肺损伤短期后遗症的发病机制，并评估是否使用抗氧化剂 N-乙酰半胱氨酸 (NAC) 可以使用暴露于 Cl2 的精确切割肺切片 (PCLS) 来抵消这些损伤。Sprague-Dawley 大鼠的肺充满琼脂糖溶液并切成 250 µm 厚的切片，暴露于 Cl2 (20-600 ppm) 并孵育 30 分钟。组织切片在暴露于 Cl2 之前用 NAC (5-25 mM) 预处理。5 小时后通过测量培养基或肺组织匀浆中的 LDH、WST-1 和炎症介质（IL-1β、IL-6 和 CINC-1）来分析毒理学反应。暴露于 Cl2 在培养基中诱导浓度依赖性细胞毒性（LDH/WST-1）和 IL-1β 释放。在组织匀浆中检测到类似的细胞因子反应。使用电场刺激法测量较大气道的收缩，200 ppm 和对照切片具有相似的收缩水平 (39 ± 5%) 但在 400 ppm Cl2 组中，诱发收缩较小 (7 ± 3%) 可能是由于到组织损伤。NAC 处理提高了细胞活力并减少了组织损伤，并且在 NAC 处理的 Cl2 暴露切片中，收缩与对照水平 (50 ± 11%) 相似。总之，Cl2 诱导了浓度依赖性肺组织损伤，而 NAC 预处理可以有效地防止这种损伤。