PMID- 28743514
OWN - NLM
STAT- MEDLINE
DCOM- 20170911
LR  - 20180122
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 389
DP  - 2017 Aug 15
TI  - Precision cut lung slices as test system for candidate therapeutics in 
      organophosphate poisoning.
PG  - 94-100
LID - S0300-483X(17)30200-7 [pii]
LID - 10.1016/j.tox.2017.07.011 [doi]
AB  - Standard therapeutic options in organophosphate (OP) poisoning are limited to the 
      administration of atropine and oximes, a regimen often lacking in efficacy and 
      applicability. Treatment alternatives are needed, preferably covering a broad 
      spectrum of OP intoxications. Although recent research yielded several promising 
      compounds, e.g. bioscavengers, modulators of the muscarinic acetylcholine (ACh) 
      receptor or bispyridinium non-oximes, these substances still need further 
      evaluation, especially regarding effects on the potentially lethal respiratory 
      symptoms of OP poisoning. Aim of this study was the development of an applicable 
      and easy method to test the therapeutic efficiency of such substances. For this 
      purpose, airway responsiveness in viable precision cut lung slices (PCLS) from 
      rats was analysed. We showed that ACh-induced airway contractions were 
      spontaneously reversible in non-poisoned PCLS, whereas in OP poisoned PCLS, 
      contractions were irreversible. This effect could be antagonized by addition of 
      the standard therapeutic atropine, thereby presenting a clear indication for 
      treatment efficiency. Now, candidate therapeutic compounds can be evaluated, 
      based on their ability to counteract the irreversible airway contraction in OP 
      poisoned PCLS.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Herbert, Julia
AU  - Herbert J
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 
      Munich, Germany.
FAU - Thiermann, Horst
AU  - Thiermann H
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 
      Munich, Germany.
FAU - Worek, Franz
AU  - Worek F
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 
      Munich, Germany.
FAU - Wille, Timo
AU  - Wille T
AD  - Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 
      Munich, Germany. Electronic address: timowille@bundeswehr.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170722
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Antidotes)
RN  - 0 (Bronchodilator Agents)
RN  - 0 (Muscarinic Antagonists)
RN  - 0 (Nerve Agents)
RN  - 0 (Organophosphates)
RN  - 7C0697DR9I (Atropine)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Antidotes/*pharmacology
MH  - Atropine/*pharmacology
MH  - Bronchoconstriction/*drug effects
MH  - Bronchodilator Agents/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Discovery/*methods
MH  - Lung/*drug effects/physiopathology
MH  - Male
MH  - Muscarinic Antagonists/*pharmacology
MH  - Muscle Contraction/*drug effects
MH  - Muscle, Smooth/*drug effects/physiopathology
MH  - Nerve Agents/*toxicity
MH  - Organophosphate Poisoning/*drug therapy/physiopathology
MH  - Organophosphates/*toxicity
MH  - Rats, Wistar
MH  - Time Factors
MH  - Tissue Culture Techniques
MH  - Tissue Survival
OTO - NOTNLM
OT  - Chemical warfare agents
OT  - Lung
OT  - Nerve agents
OT  - PCLS
OT  - Pesticide
OT  - Precision cut lung slices
EDAT- 2017/07/27 06:00
MHDA- 2017/09/12 06:00
CRDT- 2017/07/27 06:00
PHST- 2017/05/23 00:00 [received]
PHST- 2017/07/14 00:00 [revised]
PHST- 2017/07/18 00:00 [accepted]
PHST- 2017/07/27 06:00 [pubmed]
PHST- 2017/09/12 06:00 [medline]
PHST- 2017/07/27 06:00 [entrez]
AID - S0300-483X(17)30200-7 [pii]
AID - 10.1016/j.tox.2017.07.011 [doi]
PST - ppublish
SO  - Toxicology. 2017 Aug 15;389:94-100. doi: 10.1016/j.tox.2017.07.011. Epub 2017 Jul 
      22.