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N-acetyl cysteine protects against chlorine-induced tissue damage in an ex vivo model.

N-乙酰半胱氨酸在离体模型中保护免受氯诱导的组织损伤。

  • 影响因子:3.36
  • DOI:10.1016/j.toxlet.2020.01.006
  • 作者列表:"Ågren L","Elfsmark L","Akfur C","Hägglund L","Ekstrand-Hammarström B","Jonasson S
  • 发表时间:2020-01-18
Abstract

: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.

摘要

: 高浓度的氯 (Cl2) 可导致危及生命的肺损伤,本研究的目的是了解 Cl2-诱导的短期后遗症的发病机制,并评估抗氧化剂 N-乙酰半胱氨酸是否肺损伤 (NAC) 可以抵消这些损伤使用 Cl2-暴露的精确切割肺切片 (PCLS)。用琼脂糖溶液填充 Sprague-Dawley 大鼠的肺,切成 250 μ m 厚的切片,暴露于 Cl2 (20-600 ppm),孵育 30 min。在暴露于 cl2 之前,用 NAC (5-25 mM) 预处理组织切片。5 h 后通过测定培养基或肺组织匀浆中 LDH 、 WST-1 和炎症介质 (il-1 β 、 IL-6 和 CINC-1) 分析毒理学反应。Cl2 暴露诱导了浓度依赖性细胞毒性 (LDH/WST-1) 和 il-1 β 在培养基中的释放。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 和对照切片的收缩水平相似 (39 ± 5%),但在 400 ppm Cl2 组, 诱发收缩较小 (7 ± 3%),可能是由于组织损伤。NAC 处理提高了细胞活力,减少了组织损伤,在 NAC 处理的 Cl2-暴露的切片中,收缩水平与对照水平 (50 ± 11%) 相似。总之,Cl2 诱导了一种浓度依赖性肺组织损伤,用 NAC 预处理可有效防止这种损伤。因此,迫切需要改进急性肺损伤的内科治疗方法,该方法为识别和检验 Cl2-诱导的肺损伤治疗的新概念提供了一条途径。

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影响因子:3.94
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DOI:10.1016/j.taap.2019.114847
作者列表:["Bernstein DM","Toth B","Rogers RA","Kling DE","Kunzendorf P","Phillips JI","Ernst H"]

METHODS::The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.

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影响因子:4.04
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DOI:10.1042/BST20191010
作者列表:["Zaragosi LE","Deprez M","Barbry P"]

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