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

Author(s):Show less -

Sartim, Marco Aurelio ^[1] ; Souza, Camila O. S. ^[1] ; Diniz, Cassiano Ricardo A. F. ^[2] ; da Fonseca, Vanessa M. B. ^[3] ; Sousa, Lucas O. ^[1] ; Peti, Ana Paula F. ^[1] ; Costa, Tassia Rafaella ^[1] ; Lourenco, Alan G. ^[4] ; Borges, Marcos C. ^[3] ; Sorgi, Carlos A. ^[1] ; Faccioli, Lucia Helena ^[1] ; Sampaio, Suely Vilela ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Clin Anal Toxicol & Food Sci, Sch Pharmaceut Sci Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Sch Dent Ribeirao Preto, Dept Basic & Oral Biol, BR-14040904 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: BIOMOLECULES; v. 10, n. 5 MAY 2020.
• Web of Science Citations: 0

Abstract

Respiratory compromise in Crotalus durissus terrificus (C.d.t.) snakebite is an important pathological condition. Considering that crotoxin (CTX), a phospholipase A(2) 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. (AU)

• FAPESP's process: 15/06290-6 - Evaluation of anti-inflammatory potential of crotoxin, a phospholipase A2 isolated from Crotalus durissus terrificus venom, in a disseminated intravascular coagulation model induced by endotoxemia
• Grantee: Marco Aurélio Sartim
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis
• Grantee: Suely Vilela
• Support Opportunities: Research Projects - Thematic Grants