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Neutralization of snake venom phospholipase A2 toxins by aqueous extract of Casearia sylvestris (Flacourtiaceae) in mouse neuromuscular preparation
Authors:Walter LG Cavalcante  Tayná O Campos  Maeli Dal Pai-Silva  Paulo S Pereira  Clayton Z Oliveira  Andreimar M Soares  Márcia Gallacci
Institution:1. Departamento de Farmacologia, Instituto de Biociências, Universidade Estadual Paulista, UNESP, Botucatu, SP, Brazil;2. Departamento de Morfologia, Instituto de Biociências, Universidade Estadual Paulista, UNESP, Botucatu, SP, Brazil;3. Unidade de Biotecnologia, Universidade de Ribeirão Preto, UNAERP, Ribeirão Preto, SP, Brazil;4. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas, Universidade São Paulo, USP, Ribeirão Preto, SP, Brazil
Abstract:Aqueous extract of Casearia sylvestris (Flacourtiaceae) has been shown to inhibit enzymatic and biological properties of some Bothrops and Crotalus venoms and their purified phospholipase A2 (PLA2) toxins. In this work we evaluated the influence of C. sylvestris aqueous extract upon neuromuscular blocking and muscle damaging activities of some PLA2s (crotoxin from C. durissus terrificus, bothropstoxin-I from B. jararacussu, piratoxin-I from B. pirajai and myotoxin-II from B. moojeni) in mouse phrenic-diaphragm preparations. Crotoxin (0.5 μM) and all other PLA2 toxins (1.0 μM) induced irreversible and time-dependent blockade of twitches. Except for crotoxin, all PLA2 toxins induced significant muscle damage indices, assessed by microscopic analysis. Preincubation of bothropstoxin-I, piratoxin-I or myotoxin-II with C. sylvestris extract (1:5 (w/w), 30 min, 37 °C) significantly prevented the neuromuscular blockade of preparations exposed to the mixtures for 90 min; the extent of protection ranged from 93% to 97%. The vegetal extract also neutralized the muscle damage (protection of 80–95%). Higher concentration of the C. sylvestris extract (1:10, w/w) was necessary to neutralize by 90% the neuromuscular blockade induced by crotoxin. These findings expanded the spectrum of C. sylvestris antivenom activities, evidencing that it may be a good source of potentially useful PLA2 inhibitors.
Keywords:Plant medicinal  Casearia sylvestris  Plant antivenom  Snake venoms  Phospholipases A2  Neuromuscular junction
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