Potential action of the phospholipase A2 inhibitor varespladib (LY-315920) on the systemic aspects of the envenomation by Micrurus corallinus coralsnake in rats

• Grant number: 20/14191-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2021
• End date: July 31, 2022
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal Investigator: Rafael Stuani Floriano
• Grantee: Matheus Zanutto Gaspar
• Host Institution: Pró-Reitoria de Pesquisa e Pós-Graduação. Universidade do Oeste Paulista (UNOESTE). Presidente Prudente , SP, Brazil

Abstract

Envenomation by Micrurus spp. (Elapidae) is characterized by potent peripheral neurotoxicity and hypotensive activity, including other effects such as pain, oedema, nephrotoxicity and haemorrhage. The treatement is conditioned to serum therapy and there are few reports related to other therapeutic strategies. Recent studies have demonstrated that varespladib (a phospholipase A2 'PLA2' inhibitor) can be used as a potential supporting agent to serum therapy in envenomations by Viperidae and Elapidae snakes, however, its action on the envenomation by coral snakes has been poorly investigated. In this project, we aim to assess the efficiency of varespladib (VPL), associated or not to anti-elapidic serum (AES), to reduce the systemic effects induced by Micrurus corallinus coralsnake venom in rats. The animals will be divided in six experimental groups: (1) control 'saline' (2) VPL, (3) M. corallinus venom, (4) M. corallinus venom + AES, (5) M. corallinus venom + VPL (6) M. corallinus venom + AES + VPL [administration via: venom 1.5 mg/kg (intramuscular), AES ratio 1:1,5 (v/w) (intraperitoneal), VPL 0.5 mg/kg (intraperitoneal)]; AES and VPL will be administrated subsequently to venom in order to assess their neutralizing action under the acute envenomation induced by M. corallinus in rats. The animals will be clinically monitored (auricular temperature, ambulation, local oedema formation and occurrence of hemorrhage) during 120 min at intervals T0 (basal), T30, T60, T90 and T120 min, including the assessment of cardiovascular parameters through echocardiographic recording (T120 min), followed by euthanasia and blood samples collection for hemostatic (coagulation time for prothrombin and activated partial thromboplastin) e biochemical analysis (creatine kinase 'CK', creatinine 'Cr' and alanine aminotransferase 'ALT'); tissue samples of heart, kidneys, liver and contralateral gastrocnemius muscle (hind limbs) will also be collected for histopathology. The results of this study will contribute with further enhancing the knowledge about the therapeutic viability of the varespladib, associated or not to antivenom, on the systemic effects induced by Micrurus venoms.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVA-CARVALHO, ROSIMEIRE; GASPAR, MATHEUS Z.; QUADROS, LUIZ H. B.; LOBO, LUIS G. G.; ROGERIO, LETICIA M.; SANTOS, NAJLA T. S.; ZERBINATTI, MARIA C.; SANTAREM, CECILIA L.; SILVA, ELISANGELA O.; GEREZ, JULIANA R.; et al. In vivo treatment with varespladib, a phospholipase A(2) inhibitor, prevents the peripheral neurotoxicity and systemic disorders induced by Micrurus corallinus (coral snake) venom in rats. Toxicology Letters, v. 356, p. 10-pg., 2022-03-01. (20/04287-6, 20/14191-6)

SILVA-CARVALHO, ROSIMEIRE; GASPAR, MATHEUS Z.; QUADROS, LUIZ H. B.; LOBO, LUIS G. G.; SANTAR, CECILIA L.; SILVA, ELISANGELA O.; GEREZ, JULIANA R.; SILVA JR, NELSON J.; HYSLOP, STEPHEN; LOMONTE, BRUNO; et al.

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

. Toxicon, v. 213, p. 6-pg., 2022-07-15. (20/14191-6, 20/04287-6)

GASPAR, MATHEUS Z.; YABUNAKA, ANA C.; SILVA-CARVALHO, ROSIMEIRE; NASCIMENTO, CHARLES U.; BRINHOLI, REJANE B.; SILVA, ELISANGELA O.; GEREZ, JULIANA R.; SILVA JR, NELSON J.; TORRES-BONILLA, KRISTIAN A.; HYSLOP, STEPHEN; et al. Cardiac Effects of Micrurus corallinus and Micrurus dumerilii carinicauda (Elapidae) Venoms and Neutralization by Brazilian Coralsnake Antivenom and Varespladib. Cardiovascular Toxicology, v. 23, n. 3-4, p. 15-pg., 2023-02-22. (16/11344-0, 20/14191-6, 20/04287-6)