Crotoxin-Induced Mice Lung Impairment: Role of Nicotinic Acetylcholine Receptors and COX-Derived Prostanoids
| Autor: | Cassiano R.A.F. Diniz, Carlos Arterio Sorgi, Marco A. Sartim, Camila O S Souza, Vanessa M. B. Fonseca, Tássia Rafaella Costa, Lúcia Helena Faccioli, Suely Vilela Sampaio, Ana Paula Ferranti Peti, Marcos C. Borges, Alan Grupioni Lourenço, Lucas Oliveira Sousa |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Bronchoconstriction lcsh:QR1-502 Snake Bites lipid mediators Pharmacology Receptors Nicotinic Biochemistry Dinoprostone Article lcsh:Microbiology 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Phospholipase A2 COBRAS neuromuscular blocker Medicine Animals Respiratory system Molecular Biology Lung Acetylcholine receptor snake venom biology business.industry crotoxin inflammatory response Nicotinic acetylcholine receptor 030104 developmental biology medicine.anatomical_structure Nicotinic agonist lung impairment chemistry biology.protein Cholinergic Cytokines Hexamethonium business Respiratory Insufficiency 030217 neurology & neurosurgery |
| Zdroj: | Biomolecules, Vol 10, Iss 794, p 794 (2020) Biomolecules Volume 10 Issue 5 Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | Respiratory compromise in Crotalus durissus terrificus (C.d.t.) snakebite is an important pathological condition. Considering that crotoxin (CTX), a phospholipase A2 from C.d.t. venom, is the main component of the venom, the present work investigated the toxin effects on respiratory failure. Lung mechanics, morphology and soluble markers were evaluated from Swiss male mice, and mechanism determined using drugs/inhibitors of eicosanoids biosynthesis pathway and autonomic nervous system. Acute respiratory failure was observed, with an early phase (within 2 h) characterized by enhanced presence of eicosanoids, including prostaglandin E2, that accounted for the increased vascular permeability in the lung. The alterations of early phase were inhibited by indomethacin. The late phase (peaked 12 h) was marked by neutrophil infiltration, presence of pro-inflammatory cytokines/chemokines, and morphological alterations characterized by alveolar septal thickening and bronchoconstriction. In addition, lung mechanical function was impaired, with decreased lung compliance and inspiratory capacity. Hexamethonium, a nicotinic acetylcholine receptor antagonist, hampered late phase damages indicating that CTX-induced lung impairment could be associated with cholinergic transmission. The findings reported herein highlight the impact of CTX on respiratory compromise, and introduce the use of nicotinic blockers and prostanoids biosynthesis inhibitors as possible symptomatic therapy to Crotalus durissus terrificus snakebite. |
| Databáze: | OpenAIRE |
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