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Crotoxin-Induced Mice Lung Impairment: Role of Nicotinic Acetylcholine Receptors and COX-Derived Prostanoids.
- Source :
-
Biomolecules [Biomolecules] 2020 May 20; Vol. 10 (5). Date of Electronic Publication: 2020 May 20. - Publication Year :
- 2020
-
Abstract
- Respiratory compromise in Crotalus durissus terrificus (C.d.t.) snakebite is an important pathological condition. Considering that crotoxin (CTX), a phospholipase A <subscript>2</subscript> 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.
- Subjects :
- Animals
Bronchoconstriction
Cytokines metabolism
Lung drug effects
Lung pathology
Lung physiopathology
Male
Mice
Respiratory Insufficiency etiology
Respiratory Insufficiency physiopathology
Snake Bites complications
Crotoxin toxicity
Dinoprostone metabolism
Receptors, Nicotinic metabolism
Respiratory Insufficiency metabolism
Snake Bites metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2218-273X
- Volume :
- 10
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Biomolecules
- Publication Type :
- Academic Journal
- Accession number :
- 32443924
- Full Text :
- https://doi.org/10.3390/biom10050794