PMID- 34118312
OWN - NLM
STAT- MEDLINE
DCOM- 20210719
LR  - 20240226
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 349
DP  - 2021 Oct 1
TI  - High concentrations of ammonia induced cytotoxicity and bronchoconstriction in a 
      precision-cut lung slices rat model.
PG  - 51-60
LID - S0378-4274(21)00146-6 [pii]
LID - 10.1016/j.toxlet.2021.06.001 [doi]
AB  - Exposure to high concentrations of ammonia (NH(3)) can cause life-threatening 
      lung damages. The objective of this study was to establish a translational in 
      vitro model for NH(3)-induced lung injury. Precision-cut lung slices (PCLS) from 
      rats were exposed to NH(3) and toxicological responses and cell viability were 
      quantified by analysis of LDH, WST-1, inflammatory mediators (IL-1beta, IL-6, 
      CINC-1, MMP-9, RAGE and IL-18), and by microscopic evaluation of 
      bronchoconstriction induced by electric-field-stimulation (EFS) or methacholine 
      (MCh). Different treatment strategies were assessed to prevent or reverse the 
      damages caused by NH(3) using anti-inflammatory, anti-oxidant or neurologically 
      active drugs. Exposure to NH(3) caused a concentration-dependent increase in 
      cytotoxicity (LDH/WST-1) and IL-1beta release in PCLS medium. None of the treatments 
      reduced cytotoxicity. Deposition of NH(3) (24-59 mM) on untreated PCLS elicited 
      an immediate concentration-dependent bronchoconstriction. Unlike MCh, the EFS 
      method did not constrict the airways in PCLS at 5 h after NH(3)-exposure (47-59 
      mM). Atropine and TRP-channel antagonists blocked EFS-induced bronchoconstriction 
      but these inhibitors could not block the immediate NH(3)-induced 
      bronchoconstriction. In conclusion, NH(3) exposure caused cytotoxic effects and 
      lung damages in a concentration-dependent manner and this PCLS method offers a 
      way to identify and test new concepts of medical treatments and biomarkers that 
      may be of prognostic value.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
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 - 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 - 20210609
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Inflammation Mediators)
RN  - 7664-41-7 (Ammonia)
SB  - IM
MH  - Acute Lung Injury/*chemically induced/metabolism/pathology/physiopathology
MH  - Ammonia/*toxicity
MH  - Animals
MH  - Bronchoconstriction/*drug effects
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - In Vitro Techniques
MH  - Inflammation Mediators/metabolism
MH  - Lung/*drug effects/metabolism/pathology/physiopathology
MH  - Rats, Sprague-Dawley
MH  - Rats
OTO - NOTNLM
OT  - Ammonia
OT  - Bronchoconstriction
OT  - Cytotoxicity
OT  - Lung damage
OT  - Precision-cut lung slices (PCLS)
COIS- Declaration of Competing Interest The authors report no declarations of interest.
EDAT- 2021/06/13 06:00
MHDA- 2021/07/20 06:00
CRDT- 2021/06/12 20:09
PHST- 2021/01/29 00:00 [received]
PHST- 2021/05/26 00:00 [revised]
PHST- 2021/06/07 00:00 [accepted]
PHST- 2021/06/13 06:00 [pubmed]
PHST- 2021/07/20 06:00 [medline]
PHST- 2021/06/12 20:09 [entrez]
AID - S0378-4274(21)00146-6 [pii]
AID - 10.1016/j.toxlet.2021.06.001 [doi]
PST - ppublish
SO  - Toxicol Lett. 2021 Oct 1;349:51-60. doi: 10.1016/j.toxlet.2021.06.001. Epub 2021 
      Jun 9.