Involvement of phospholipase A 2 in the neuromuscular blockade caused by coralsnake (Micrurus spp.) venoms in mouse phrenic nerve-diaphragm preparations in vitro.

Autor: Couceiro FYGM; Laboratory of Toxinology and Cardiovascular Research, Graduate Program in Health Sciences, University of Western São Paulo (UNOESTE), Presidente Prudente, SP, Brazil., Demico PJ; Laboratory of Toxinology and Cardiovascular Research, Graduate Program in Health Sciences, University of Western São Paulo (UNOESTE), Presidente Prudente, SP, Brazil., Dias SR; Laboratory of Toxinology and Cardiovascular Research, Graduate Program in Health Sciences, University of Western São Paulo (UNOESTE), Presidente Prudente, SP, Brazil., Oliveira IN; Laboratory of Toxinology and Cardiovascular Research, Graduate Program in Health Sciences, University of Western São Paulo (UNOESTE), Presidente Prudente, SP, Brazil., Pacagnelli FL; Laboratory of Toxinology and Cardiovascular Research, Graduate Program in Health Sciences, University of Western São Paulo (UNOESTE), Presidente Prudente, SP, Brazil., Silva EO; Laboratory of Pathological Anatomy, Veterinary Hospital, University of Western São Paulo (UNOESTE), Presidente Prudente, SP, Brazil., Sant'Anna SS; Laboratory of Herpetology, Butantan Institute (IB), São Paulo, SP, Brazil., Grego KF; Laboratory of Herpetology, Butantan Institute (IB), São Paulo, SP, Brazil., Morais-Zani K; Laboratory of Herpetology, Butantan Institute (IB), São Paulo, SP, Brazil., Torres-Bonilla KA; Section of Pharmacology, Department of Translational Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil., Hyslop S; Section of Pharmacology, Department of Translational Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil., Floriano RS; Laboratory of Toxinology and Cardiovascular Research, Graduate Program in Health Sciences, University of Western São Paulo (UNOESTE), Presidente Prudente, SP, Brazil. Electronic address: rafael@unoeste.br.
Jazyk: angličtina
Zdroj: Toxicon : official journal of the International Society on Toxinology [Toxicon] 2023 Oct; Vol. 234, pp. 107263. Date of Electronic Publication: 2023 Sep 01.
DOI: 10.1016/j.toxicon.2023.107263
Abstrakt: In this work, we examined the neuromuscular blockade caused by venoms from four South-American coralsnakes (Micrurus altirostris - MA, M. corallinus - MC, M. spixii - MS, and M. dumerilii carinicauda - MDC) and the ability of varespladib (VPL), a phospholipase A 2 (PLA 2 ) inhibitor, to attenuate this blockade. PLA 2 activity was determined using a colorimetric assay and a fixed amount of venom (10 μg). Neurotoxicity was assayed using a single concentration of venom (10 μg/ml) in mouse phrenic nerve-diaphragm (PND) preparations mounted for myographic recordings and then subjected to histological analysis. All venoms showed PLA 2 activity, with MS and MA venoms having the highest (15.53 ± 1.9 A 425 nm /min) and lowest (0.23 ± 0.14 A 425 nm /min) activities, respectively. VPL (292 and 438 μM) inhibited the PLA 2 activity of all venoms, although that of MA venom was least affected. All venoms caused neuromuscular blockade, with MS and MDC venoms causing the fastest and slowest 100% blockade [in 40 ± 3 min and 120 ± 6 min (n = 4), respectively]; MA and MC produced complete blockade within 90-100 min. Preincubation of venoms with 292 μM VPL attenuated the blockade to varying degrees: the greatest inhibition was seen with MDC venom and blockade by MS venom was unaffected by this inhibitor. These results indicate that PLA 2 has a variable contribution to coralsnake venom-induced neuromuscular blockade in vitro, with the insensitivity of MS venom to VPL suggesting that blockade by this venom is mediated predominantly by post-synaptically-active α-neurotoxins.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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