Efficacy of atropine and scopolamine on airway contractions following exposure to the nerve agent VX

Organophosphorus pesticides exhibit compound specific effects in rat precision-cut lung slices (PCLS): mechanisms involved in airway response, cytotoxicity, inflammatory activation and antioxidative defense

“…OP exposure without ACh did not result in an alteration of the airway area in the highest applied concentrations (control: 102 ± 3%; parathion: 113 ± 3%; paraoxon: 98 ± 4%; malathion: 104 ± 3%; malaoxon: 109 ± 8%). In addition, maximum constriction of the airway after ACh addition was not significantly different between the four tested OP in the highest applied concentrations (airway area after ACh addition: control: 53 ± 9%; parathion: 51 ± 12%; paraoxon: 45 ± 9%; malathion: 46 ± 10%; malaoxon: 50 ± 8%) and is comparable with other PCLS studies (Wigenstam et al 2021 ; Herbert et al 2017 ). Exposure with parathion or malathion in concentrations between 0.1 and 100 µmol/L had no significant effect on airway relaxation compared to the solvent control [mean relaxation efficiency 100 µmol/L: parathion (118%, Fig.…”

“…Addition of the OP without ACh stimulation failed to induce airway constriction, most probably due to limited nervous stimulation in the PCLS. This was also observed in VX-exposed PCLS (Herbert et al 2017;Wigenstam et al 2021). We did not observe significant differences in maximum constriction of the airways between the four applied OP.…”

“…We did not observe significant differences in maximum constriction of the airways between the four applied OP. However, in a PCLS study from Wigenstam et al ( 2021 ), using a slightly different exposure scenario (ACh-OP-ACh instead of OP-ACh), nerve agent exposure in combination with ACh led to an increased bronchoconstriction in PCLS compared to ACh alone. The parent OP parathion and malathion failed to induce an inhibitory effect on airway relaxation, indicating that AChE activity is not impaired (Fig.…”

“…The constriction is spontaneously reversible due to lung resident AChE activity, which results in relaxation of the airways. Airway response upon OP exposure has previously been studied to find novel treatment strategies in OP poisoning (Herbert et al 2017(Herbert et al , 2019Wigenstam et al 2021). Addition of the OP without ACh stimulation failed to induce airway constriction, most probably due to limited nervous stimulation in the PCLS.…”

Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery

“…Since then, an array of other endpoints have been studied to understand how exposure to various toxicants can engender inflammation and even promote airway hyperresponsiveness. Consequences of exposure to noxious gases, including warfare agents like sarin and VX gas, in PCLS showed enhanced airway constriction that could be modulated by anti-muscarinic drugs [ 236 – 239 ]. Chlorine exposure of PCLS increased release of inflammatory mediators from the tissue, decreased airway constriction, and decreased cell viability [ 240 , 241 ].…”