title: Ultrastructural aspects of mouse nerve-muscle preparation exposed to Bothrops jararacussu and Bothrops bilineatus venoms and their toxins BthTX-I and Bbil-TX: Unknown myotoxic effects.
abstract: Bites by Bothrops snakes normally induce local pain, haemorrhage, oedema and myonecrosis. Mammalian isolated nerve-muscle preparations exposed to Bothrops venoms and their phospholipase A2toxins (PLA2) can exhibit a neurotoxic pattern as increase in frequency of miniature end-plate potentials (MEPPs) as well as in amplitude of end-plate potentials (EPPs); neuromuscular facilitation followed by complete and irreversible blockade without morphological evidence for muscle damage. In this work, we analysed the ultrastructural damage induced by Bothrops jararacussu and Bothrops bilineatus venoms and their PLA2toxins (BthTX-I and Bbil-TX) in mouse isolated nerve-phrenic diaphragm preparations (PND). Under transmission electron microscopy (TEM), PND preparations previously exposed to B. jararacussu and B. bilineatus venoms and BthTX-I and Bbil-TX toxins showed hypercontracted and loosed myofilaments; unorganized sarcomeres; clusters of edematous sarcoplasmic reticulum and mitochondria; abnormal chromatin distribution or apoptotic-like nuclei. The principal affected organelles, mitochondria and sarcoplasmic reticulum, were those related to calcium buffering and, resulting in sarcomeres and myofilaments hypercontraction. Schwann cells were also damaged showing edematous axons and mitochondria as well as myelin sheath alteration. These ultrastructural changes caused by both of Bothrops venoms and toxins indicate that the neuromuscular blockade induced by them in vitro can also be associated with nerve and muscle degeneration.
authors.affiliation: Multidisciplinary Research Laboratory, São Francisco University (USF), Av. São Francisco de Assis, 218, Zip Code 12916-900, Bragança Paulista, SP, Brazil.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Melaré
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Zip Code 13083-887, Campinas, SP, Brazil.
authors.forename: Rafael Stuani
authors.initials: RS
authors.lastname: Floriano
authors.affiliation: Multidisciplinary Research Laboratory, São Francisco University (USF), Av. São Francisco de Assis, 218, Zip Code 12916-900, Bragança Paulista, SP, Brazil.
authors.forename: Marta
authors.initials: M
authors.lastname: Gracia
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, Zip Code 13083-887, Campinas, SP, Brazil.
authors.forename: Léa
authors.initials: L
authors.lastname: Rodrigues-Simioni
authors.affiliation: Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Zip Code 13083-862, Campinas, SP, Brazil.
authors.forename: Maria Alice da
authors.initials: MA
authors.lastname: Cruz-Höfling
authors.affiliation: Multidisciplinary Research Laboratory, São Francisco University (USF), Av. São Francisco de Assis, 218, Zip Code 12916-900, Bragança Paulista, SP, Brazil. thalita.rocha@usf.edu.br.|Department of Biochemistry and Tissue Biology, Institute of Biology, State University of Campinas (UNICAMP), Rua Monteiro Lobato, 255, Zip Code 13083-862, Campinas, SP, Brazil. thalita.rocha@usf.edu.br.
authors.forename: Thalita
authors.initials: T
authors.lastname: Rocha
mesh_terms: D000818:Animals; D017837:Bothrops; D003435:Crotalid Venoms / Q000633:toxicity*; D003964:Diaphragm / Q000187:drug effects* / Q000648:ultrastructure; D054501:Group II Phospholipases A2 / Q000633:toxicity*; D008297:Male; D051379:Mice; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000648:ultrastructure*; D010791:Phrenic Nerve / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: D003435:Crotalid Venoms; C078097:bothropstoxin; D054501:Group II Phospholipases A2; C072031:bothropstoxin II
keywords: Asp49-PLA2; Bothrops venoms; Lys49-PLA2; myotoxicity; transmission electron microscopy