Partial efficacy of a Brazilian coralsnake antivenom and varespladib in neutralizing distinct toxic effects induced by sublethal Micrurus dumerilii carinicauda envenoming in rats

Rosimeire Silva-Carvalho; Matheus Z Gaspar; Luiz H B Quadros; Luís G G Lobo; Rogério Giuffrida; Cecília L Santarém; Elisangela O Silva; Juliana R Gerez; Nelson J Silva Jr; Stephen Hyslop; Bruno Lomonte; Rafael S Floriano

doi:10.1016/j.toxicon.2022.04.014

Partial efficacy of a Brazilian coralsnake antivenom and varespladib in neutralizing distinct toxic effects induced by sublethal Micrurus dumerilii carinicauda envenoming in rats

Toxicon. 2022 Jul 15:213:99-104. doi: 10.1016/j.toxicon.2022.04.014. Epub 2022 Apr 27.

Affiliations

¹ Laboratory of Toxinology and Cardiovascular Research, Graduate Program in Health Sciences, University of Western São Paulo, Rodovia Raposo Tavares Km 572, B2-205, 19067-175, Presidente Prudente, SP, Brazil.
² Graduate Program in Animal Sciences, University of Western São Paulo, Rodovia Raposo Tavares Km 572, 19067-175, Presidente Prudente, SP, Brazil.
³ Department of Histology, State University of Londrina (UEL), Rodovia Celso Garcia Cid Km 380, 86057-970, Londrina, PR, Brazil.
⁴ Graduate Program in Environmental Sciences and Health, School of Medical, Pharmaceutical and Biomedical Sciences, Pontifical Catholic University of Goiás (PUC-Goiás), 74605-140, Goiânia, GO, Brazil.
⁵ Section of Pharmacology, Department of Translational Medicine, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Rua Tessália Vieira de Camargo, 126, 13083-887, Campinas, SP, Brazil.
⁶ Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, 11501, San José, Costa Rica. Electronic address: bruno.lomonte@ucr.ac.cr.
⁷ Laboratory of Toxinology and Cardiovascular Research, Graduate Program in Health Sciences, University of Western São Paulo, Rodovia Raposo Tavares Km 572, B2-205, 19067-175, Presidente Prudente, SP, Brazil. Electronic address: rafael@unoeste.br.

PMID: 35489427
DOI: 10.1016/j.toxicon.2022.04.014

Abstract

In this work, we reported the efficacy of a combination of Brazilian therapeutic coralsnake antivenom (CAV) and varespladib (phospholipase A₂ inhibitor - VPL) in partially neutralizing selected toxic effects of Micrurus dumerilii carinicauda coralsnake venom in rats. Venom caused local myonecrosis and systemic neurotoxicity, nephrotoxicity, and hepatotoxicity within 2 h of injection. CAV and VPL administered separately failed to prevent most of these alterations. However, a combination of CAV plus VPL offered variable protection against venom-induced coagulation disturbances, leukocytosis, and renal-hepatic morphological alterations.

Keywords: Antivenom; Coralsnake venom; Neutralization; Systemic envenomation; Varespladib.

MeSH terms

Acetates
Animals
Antivenins / pharmacology
Brazil
Coral Snakes*
Elapid Venoms / toxicity
Indoles
Keto Acids
Rats

Substances

Acetates
Antivenins
Elapid Venoms
Indoles
Keto Acids
varespladib