Biomolecules (May 2020)

Crotoxin-Induced Mice Lung Impairment: Role of Nicotinic Acetylcholine Receptors and COX-Derived Prostanoids

  • Marco Aurelio Sartim,
  • Camila O. S. Souza,
  • Cassiano Ricardo A. F. Diniz,
  • Vanessa M. B. da Fonseca,
  • Lucas O. Sousa,
  • Ana Paula F. Peti,
  • Tassia Rafaella Costa,
  • Alan G. Lourenço,
  • Marcos C. Borges,
  • Carlos A. Sorgi,
  • Lucia Helena Faccioli,
  • Suely Vilela Sampaio

DOI
https://doi.org/10.3390/biom10050794
Journal volume & issue
Vol. 10, no. 5
p. 794

Abstract

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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.

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