PMID- 31962155
OWN - NLM
STAT- MEDLINE
DCOM- 20200217
LR  - 20200217
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 322
DP  - 2020 Apr 1
TI  - N-acetyl cysteine protects against chlorine-induced tissue damage in an ex vivo 
      model.
PG  - 58-65
LID - S0378-4274(20)30006-0 [pii]
LID - 10.1016/j.toxlet.2020.01.006 [doi]
AB  - High-level concentrations of chlorine (Cl(2)) can cause life-threatening lung 
      injuries and the objective in this study was to understand the pathogenesis of 
      short-term sequelae of Cl(2)-induced lung injury and to evaluate whether 
      pre-treatment with the antioxidant N-acetyl cysteine (NAC) could counteract these 
      injuries using Cl(2)-exposed precision-cut lung slices (PCLS). The lungs of 
      Sprague-Dawley rats were filled with agarose solution and cut into 250 mum-thick 
      slices that were exposed to Cl(2) (20-600 ppm) and incubated for 30 min. The 
      tissue slices were pre-treated with NAC (5-25 mM) before exposure to Cl(2). 
      Toxicological responses were analyzed after 5 h by measurement of LDH, WST-1 and 
      inflammatory mediators (IL-1beta, IL-6 and CINC-1) in medium or lung tissue 
      homogenate. Exposure to Cl(2) induced a concentration-dependent cytotoxicity 
      (LDH/WST-1) and IL-1beta 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 Cl(2) 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 Cl(2)-exposed slices. In 
      conclusion, Cl(2) 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 Cl(2)-induced lung 
      injuries.
CI  - Copyright (c) 2020. Published by Elsevier B.V.
FAU - Agren, Lina
AU  - Agren L
AD  - Swedish Defence Research Agency, CBRN Defence and Security, Umea, Sweden.
FAU - Elfsmark, Linda
AU  - Elfsmark L
AD  - Swedish Defence Research Agency, CBRN Defence and Security, Umea, Sweden.
FAU - Akfur, Christine
AU  - Akfur C
AD  - Swedish Defence Research Agency, CBRN Defence and Security, Umea, Sweden.
FAU - Hagglund, Lars
AU  - Hagglund L
AD  - Swedish Defence Research Agency, CBRN Defence and Security, Umea, Sweden.
FAU - Ekstrand-Hammarstrom, Barbro
AU  - Ekstrand-Hammarstrom B
AD  - Swedish Defence Research Agency, CBRN Defence and Security, Umea, Sweden.
FAU - Jonasson, Sofia
AU  - Jonasson S
AD  - Swedish Defence Research Agency, CBRN Defence and Security, Umea, Sweden. 
      Electronic address: sofia.jonasson@foi.se.
LA  - eng
PT  - Journal Article
DEP - 20200118
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Chemokine CXCL1)
RN  - 0 (Cxcl1 protein, rat)
RN  - 0 (IL1B protein, rat)
RN  - 0 (Il6 protein, rat)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 4R7X1O2820 (Chlorine)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*pharmacology
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Antioxidants/*pharmacology
MH  - Cell Survival/drug effects
MH  - Chemokine CXCL1/metabolism
MH  - Chlorine/*toxicity
MH  - Cytoprotection
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - In Vitro Techniques
MH  - Inflammation Mediators/*metabolism
MH  - Interleukin-1beta/metabolism
MH  - Interleukin-6/metabolism
MH  - Lung/*drug effects/metabolism/pathology/physiopathology
MH  - Lung Injury/chemically induced/metabolism/pathology/*prevention & control
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - Chlorine
OT  - Lung-injury
OT  - N-acetyl cysteine
OT  - Precision-cut lung slices (PCLS)
OT  - Rat
OT  - Treatment
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/01/22 06:00
MHDA- 2020/02/18 06:00
CRDT- 2020/01/22 06:00
PHST- 2019/09/11 00:00 [received]
PHST- 2020/01/07 00:00 [revised]
PHST- 2020/01/09 00:00 [accepted]
PHST- 2020/01/22 06:00 [pubmed]
PHST- 2020/02/18 06:00 [medline]
PHST- 2020/01/22 06:00 [entrez]
AID - S0378-4274(20)30006-0 [pii]
AID - 10.1016/j.toxlet.2020.01.006 [doi]
PST - ppublish
SO  - Toxicol Lett. 2020 Apr 1;322:58-65. doi: 10.1016/j.toxlet.2020.01.006. Epub 2020 
      Jan 18.