ction of Varespladib (LY-315920), a Phospholipase A(2) Inhibitor, on the Enzymatic, Coagulant and Haemorrhagic Activities of Lachesis muta rhombeata (South-American Bushmaster) Veno

Autor(es):Mostrar menos -

Gutierres, Pamella G. ^[1] ; Pereira, Diego R. ^[1] ; Vieira, Nataly L. ^[1] ; Arantes, Lilian F. ^[2] ; Silva, Jr., Nelson J. ^[3] ; Torres-Bonilla, Kristian A. ^[4] ; Hyslop, Stephen ^[4] ; Morais-Zani, Karen ^[5] ; Nogueira, Rosa M. B. ^[1] ; Rowan, Edward G. ^[6] ; Floriano, Rafael S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Western Sao Paulo, Lab Toxinol & Cardiovasc Res, Presidente Prudente - Brazil

^[2] Rural Fed Univ Pernambuco, Grad Program Zootech, Recife, PE - Brazil

^[3] Pontifical Catholic Univ Goias, Sch Med Pharmaceut & Biomed Sci, Grad Program Environm Sci & Hlth, Goiania, Go - Brazil

^[4] Univ Estadual Campinas, Fac Med Sci, Dept Pharmacol, Campinas - Brazil

^[5] Butantan Inst, Lab Herpetol, Sao Paulo - Brazil

^[6] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow, Lanark - Scotland

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN PHARMACOLOGY; v. 12, JAN 12 2022.
• Citações Web of Science: 0

Resumo

Varespladib (VPL) was primarily developed to treat inflammatory disturbances associated with high levels of serum phospholipase A(2) (PLA(2)). VPL has also demonstrated to be a potential antivenom support agent to prevent PLA(2)-dependent effects produced by snake venoms. In this study, we examined the action of VPL on the coagulant, haemorrhagic and enzymatic activities of Lachesis muta rhombeata (South-American bushmaster) venom. Conventional colorimetric enzymatic assays were performed for PLA(2), caseinolytic and esterasic activities; in vitro coagulant activities for prothrombin time (PT) and activated partial thromboplastin time (aPTT) were performed in rat citrated plasma through a quick timer coagulometer, whereas the dimensions of haemorrhagic haloes obtained after i.d. injections of venom in Wistar rats were determined using ImageJ software. Venom (1 mg/ml) exhibited accentuated enzymatic activities for proteases and PLA(2) in vitro, with VPL abolishing the PLA(2) activity from 0.01 mM; VPL did not affect caseinolytic and esterasic activities at any tested concentrations (0.001-1 mM). In rat citrated plasma in vitro, VPL (1 mM) alone efficiently prevented the venom (1 mg/ml)-induced procoagulant disorder associated to extrinsic (PT) pathway, whereas its association with a commercial antivenom successfully prevented changes in both intrinsic (aPTT) and extrinsic (PT) pathways; commercial antivenom by itself failed to avoid the procoagulant disorders by this venom. Venom (0.5 mg/kg)-induced hemorrhagic activity was slightly reduced by VPL (1 mM) alone or combined with antivenom (antivenom:venom ratio 1:3 `v/w') in rats, with antivenom alone producing no protective action on this parameter. In conclusion, VPL does not inhibit other major enzymatic groups of L. m. rhombeata venom, with its high PLA(2) antagonize activity efficaciously preventing the venom-induced coagulation disturbances. (AU)

• Processo FAPESP: 20/11268-8 - Avaliação da ação protetora de varespladib (LY315920), um inibidor de fosfolipase A2, sobre os efeitos hemorrágico e proteolítico do veneno de Lachesis muta rhombeata (Surucucu Sul-Americana)
• Beneficiário: Pamella Godinho Gutierres
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 21/14375-2 - Ação de varespladib (Ly-315920), um inibidor de fosfolipase A2, sobre as atividades enzimática, coagulante e hemorrágica do veneno de Lachesis muta rhombeata (Surucucu Sul-Americana)
• Beneficiário: Rafael Stuani Floriano
• Modalidade de apoio: Auxílio à Pesquisa - Publicações científicas - Artigo
• Processo FAPESP: 20/04287-6 - Caracterização estrutural e farmacológica de toxinas isoladas do veneno de Bothrops bilineatus smaragdinus (víbora de floresta) com potencial atividade moduladora da liberação sináptica motora e de funções cardiovasculares
• Beneficiário: Rafael Stuani Floriano
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular