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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Floriano, Rafael S. [1] ; Schezaro-Ramos, Raphael [1] ; Silva, Jr., Nelson J. [2] ; Bucaretchi, Fabio [3, 4] ; Rowan, Edward G. [5] ; Hyslop, Stephen [1]
Total Authors: 6
[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
Total Affiliations: 5
Document type: Journal article
Source: ARCHIVES OF TOXICOLOGY; v. 93, n. 7, p. 2065-2086, JUL 2019.
Web of Science Citations: 0

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)

FAPESP's process: 14/24409-8 - Characterization of presynaptic toxins from venom of the coral snake Micrurus lemniscatus lemniscatus
Grantee:Rafael Stuani Floriano
Support Opportunities: Scholarships in Brazil - Post-Doctoral