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Updated: Feb 25, 2026
Assessment of the Cytotoxic and Immunomodulatory Effects of Substances in Human Precision-cut Lung Slices
Published on: May 9, 2018
Precision cut lung slices as test system for candidate therapeutics in organophosphate poisoning
Julia Herbert1, Horst Thiermann1, Franz Worek1
1Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich, Germany.
Abstract:
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.
Insights
Organophosphate poisoning causes irreversible airway contractions. This study developed a method using rat lung slices to test new treatments, showing atropine can reverse these contractions, indicating therapeutic potential.
Area of Science:
- Toxicology
- Pharmacology
- Respiratory Medicine
Background:
- Organophosphate (OP) poisoning treatments like atropine and oximes have limited efficacy.
- Novel therapeutic strategies are crucial for broad-spectrum OP intoxication management.
- Evaluating new treatments for OP-induced respiratory symptoms is essential.
Purpose of the Study:
- To develop a practical method for assessing the therapeutic efficiency of novel OP poisoning treatments.
- To investigate the effects of OP poisoning on airway responsiveness.
- To establish a model for evaluating compounds targeting OP-induced respiratory distress.
Main Methods:
- Utilized precision cut lung slices (PCLS) from rats to analyze airway responsiveness.
- Induced airway contractions using acetylcholine (ACh) in both non-poisoned and OP-poisoned PCLS.
- Assessed the reversibility of ACh-induced contractions and the effect of atropine.
Main Results:
- ACh-induced airway contractions were irreversible in OP-poisoned PCLS, unlike in non-poisoned controls.
- The standard therapeutic atropine successfully antagonized the irreversible contractions in OP-poisoned PCLS.
- This model demonstrates a clear indicator of therapeutic treatment efficiency.
Conclusions:
- The PCLS model provides a viable method for evaluating new organophosphate poisoning therapies.
- Irreversible airway contraction in OP poisoning can be reversed by atropine, validating the model.
- Candidate therapeutic compounds can now be screened for their ability to counteract OP-induced airway hyperresponsiveness.
