PMID- 37820773
OWN - NLM
STAT- MEDLINE
DCOM- 20231106
LR  - 20240223
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 479
DP  - 2023 Nov 15
TI  - N-acetyl cysteine mitigates lung damage and inflammation after chlorine exposure 
      in vivo and ex vivo.
PG  - 116714
LID - S0041-008X(23)00353-8 [pii]
LID - 10.1016/j.taap.2023.116714 [doi]
AB  - The objective of this study was to explore the effects of antioxidant treatments, 
      specifically N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA), in a mouse 
      model of chlorine (Cl(2))-induced lung injury. Additionally, the study aimed to 
      investigate the utility of pig precision-cut lung slices (PCLS) as an ex vivo 
      alternative for studying the short-term effects of Cl(2) exposure and evaluating 
      antioxidant treatments. The toxicological responses were analyzed in 
      Cl(2)-exposed mice (inflammation, airway hyperresponsiveness (AHR)) and PCLS 
      (viability, cytotoxicity, inflammatory mediators). Airways contractions were 
      assessed using a small ventilator for mice and electric-field stimulation (EFS) 
      for PCLS. Antioxidant treatments were administered to evaluate their effects. In 
      Cl(2)-exposed mice, NAC treatment did not alleviate AHR, but it did reduce the 
      number of neutrophils in bronchoalveolar lavage fluid and inflammatory mediators 
      in lung tissue. In PCLS, exposure to Cl(2) resulted in concentration-dependent 
      toxicity, impairing the lung tissue's ability to respond to EFS-stimulation. NAC 
      treatment increased viability, mitigated the toxic responses caused by Cl(2) 
      exposure, and maintained contractility comparable to unexposed controls. 
      Interestingly, NACA did not provide any additional treatment effect beyond NAC in 
      both models. In conclusion, the establishment of a pig model for Cl(2)-induced 
      lung damage supports further investigation of NAC as a potential treatment. 
      However, the lack of protective effects on AHR after NAC treatment in mice 
      suggests that NAC alone may not be sufficient as a complete treatment for Cl(2) 
      injuries. Optimization of existing medications with a polypharmacy approach may 
      be more successful in addressing the complex sequelae of Cl(2)-induced lung 
      injury.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Gustafson, Asa
AU  - Gustafson A
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 - Karlsson, Terese
AU  - Karlsson T
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 - 20231010
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - WYQ7N0BPYC (Acetylcysteine)
RN  - 4R7X1O2820 (Chlorine)
RN  - 0 (Antioxidants)
RN  - 0 (Inflammation Mediators)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Swine
MH  - *Acetylcysteine/pharmacology/therapeutic use
MH  - Chlorine/toxicity
MH  - *Lung Injury/chemically induced/drug therapy/prevention & control
MH  - Antioxidants/pharmacology
MH  - Lung
MH  - Inflammation/chemically induced/drug therapy
MH  - Inflammation Mediators
OTO - NOTNLM
OT  - Antioxidants
OT  - Chlorine
OT  - Cytotoxicity
OT  - Lung damage
OT  - Precision-cut lung slices (PCLS)
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- 2023/10/12 00:43
MHDA- 2023/11/06 06:42
CRDT- 2023/10/11 19:36
PHST- 2023/08/07 00:00 [received]
PHST- 2023/09/26 00:00 [revised]
PHST- 2023/10/07 00:00 [accepted]
PHST- 2023/11/06 06:42 [medline]
PHST- 2023/10/12 00:43 [pubmed]
PHST- 2023/10/11 19:36 [entrez]
AID - S0041-008X(23)00353-8 [pii]
AID - 10.1016/j.taap.2023.116714 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2023 Nov 15;479:116714. doi: 10.1016/j.taap.2023.116714. 
      Epub 2023 Oct 10.