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

Toxicol Lett. 2020 Apr 1;322:58-65. doi: 10.1016/j.toxlet.2020.01.006. Epub 2020 Jan 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.

Keywords: Chlorine; Lung-injury; N-acetyl cysteine; Precision-cut lung slices (PCLS); Rat; Treatment.

MeSH terms

  • Acetylcysteine / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Cell Survival / drug effects
  • Chemokine CXCL1 / metabolism
  • Chlorine / toxicity*
  • Cytoprotection
  • Dose-Response Relationship, Drug
  • Female
  • In Vitro Techniques
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Lung / physiopathology
  • Lung Injury / chemically induced
  • Lung Injury / metabolism
  • Lung Injury / pathology
  • Lung Injury / prevention & control*
  • Rats, Sprague-Dawley

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Chemokine CXCL1
  • Cxcl1 protein, rat
  • IL1B protein, rat
  • Il6 protein, rat
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • Chlorine
  • Acetylcysteine