Neurotoxicity of Micrurus lemniscatus lemniscatus (South American coralsnake) venom in vertebrate neuromuscular preparations in vitro and neutralization by antivenom

Autor(es)

Floriano, Rafael S. ^[1] ; Schezaro-Ramos, Raphael ^[1] ; Silva, Jr., Nelson J. ^[2] ; Bucaretchi, Fabio ^{[3, 4]} ; Rowan, Edward G. ^[5] ; Hyslop, Stephen ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas UNICAMP, Fac Ciencias Med, Dept Farmacol, Rua Tessalia Vieira Camargo 126, BR-13083887 Campinas, SP - Brazil

^[2] Pontificia Univ Catolica Goias PUC GO, Escola Ciencias Med Farmaceut & Biomed, Programa Posgrad Ciencias Ambientais & Saude, Rua 232, 128, BR-74605140 Goiania, Go - Brazil

^[3] Univ Estadual Campinas UNICAMP, Fac Ciencias Med, Dept Pediat, Rua Tessalia Vieira Camargo 126, BR-13083887 Campinas, SP - Brazil

^[4] Univ Estadual Campinas UNICAMP, Fac Ciencias Med, Ctr Informacao & Assistencia Toxicol Campinas CIA, Rua Tessalia Vieira Camargo 126, BR-13083887 Campinas, SP - Brazil

^[5] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Cathedral St 161, Glasgow G4 0RE, Lanark - Scotland

• Tipo de documento: Artigo Científico
• Fonte: ARCHIVES OF TOXICOLOGY; v. 93, n. 7, p. 2065-2086, JUL 2019.
• Citações Web of Science: 0

Resumo

We investigated the effect of South American coralsnake (Micrurus lemniscatus lemniscatus) venom on neurotransmission in vertebrate nerve-muscle preparations in vitro. The venom (0.1-30 mu g/ml) showed calcium-dependent PLA(2) activity and caused irreversible neuromuscular blockade in chick biventer cervicis (BC) and mouse phrenic nerve-diaphragm (PND) preparations. In BC preparations, contractures to exogenous acetylcholine and carbachol (CCh), but not KCl, were abolished by venom concentrations >= 0.3 mu g/ml; in PND preparations, the amplitude of the tetanic response was progressively attenuated, but with little tetanic fade. In low Ca2+ physiological solution, venom (10 mu g/ml) caused neuromuscular blockade in PND preparations within similar to 10min that was reversible by washing; the addition of Ca2+ immediately after the blockade temporarily restored the twitch responses, but did not prevent the progression to irreversible blockade. Venom (10 mu g/ml) did not depolarize diaphragm muscle, prevent depolarization by CCh, or cause muscle contracture or histological damage. Venom (3 mu g/ml) had a biphasic effect on the frequency of miniature end-plate potentials, but did not affect their amplitude; there was a progressive decrease in the amplitude of evoked end-plate potentials. The amplitude of compound action potentials in mouse sciatic nerve was unaffected by venom (10 mu g/ml). Pre-incubation of venom with coralsnake antivenom (Instituto Butantan) at the recommended antivenom:venom ratio did not neutralize the neuromuscular blockade in PND preparations, but total neutralization was achieved with a tenfold greater volume of antivenom. The addition of antivenom after 50% and 80% blockade restored the twitch responses. These results show that M. lemniscatus lemniscatus venom causes potent, irreversible neuromuscular blockade, without myonecrosis. This blockade is apparently mediated by pre- and postsynaptic neurotoxins and can be reversed by coralsnake antivenom. (AU)

• Processo FAPESP: 14/24409-8 - Caracterização de toxinas pré-sinápticas da peçonha da coral Micrurus lemniscatus lemniscatus
• Beneficiário: Rafael Stuani Floriano
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado