Penehyclidine hydrochloride preconditioning provides pulmonary and systemic protection in a rat model of lung ischaemia reperfusion injury.

Abstract

Penehyclidine hydrochloride (PHC) is a new anticholinergic agent that provides protective effects in experimental models of heart and brain ischaemia as well as reperfusion (I/R) injury. In this study, we tested the hypothesis that PHC can alleviate lung ischaemia-reperfusion injury and improve pulmonary and systemic function in rats. PHC was administered intravenously at various doses (d= 0.1, 0.3, 1, 3 mg/kg) to I/R rats. We used six indicators, including lung function, histologic examination, pulmonary oedema, oxidative stress, inflammatory responses, and apoptosis staining to quantify the pulmonary and systemic protective effects of PHC. Haematoxylin and eosin staining was used for pulmonary histologic examination. The expression of Toll-like receptor (TLR) 4, phospho-inhibitor of NF-κB (p-IκB) and nuclear factor-kappa B (NF-κB) was analysed using western blotting. ELISA was conducted to detect inflammatory mediators. Oxidative stress markers as well as myeloperoxidase (MPO) were determined using an assay kit. PHC preconditioning (with concentrations ranging from 0.3 mg/kg to 3 mg/kg 30 min before the onset of I/R) significantly reduced lung histopathological changes, down regulated TLR4, p-IκB and NF-κB expression, and decreased inflammatory mediators as well as the total number of leukocytes and neutrophils in bronchoalveolar lavage (BAL) fluid and plasma. The lung tissue contents of reactive oxygen species (ROS), malondialdehyde (MDA), and MPO as well as pulmonary oedema formation decreased, while SOD (superoxide dismutase) activity was significantly upregulated. PHC preconditioning (with concentrations ranging from 1 mg/kg to 3 mg/kg) significantly improved the lung function and attenuated the apoptotic rate. The probable mechanism for this finding is the inhibition of proinflammatory mediators via the suppression of reactive oxygen species production and the TLR4/NF-κB signalling pathway.

• Authors: Yaguang Wang, Duomao Lin, Hongbao Tan, Yafen Gao, Jun Ma
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 839 Pg. 1-11 (Nov 15 2018) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 30201378 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Inflammation Mediators
• NF-kappa B
• Quinuclidines
• penehyclidine

Topics

• Animals
• Apoptosis (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Gene Expression Regulation (drug effects)
• Inflammation Mediators (metabolism)
• Ischemic Preconditioning
• Lung (blood supply, drug effects, metabolism, pathology)
• Male
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)
• Quinuclidines (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (metabolism, pathology, physiopathology)