Cardiac Effects of Micrurus corallinus and Micrurus dumerilii carinicauda (Elapidae) Venoms and Neutralization by Brazilian Coralsnake Antivenom and Varespladib

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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 ; Pacagnelli, Francis L. ; Floriano, Rafael S.

• Document type: Journal article
• Source: Cardiovascular Toxicology; v. 23, n. 3-4, p. 15-pg., 2023-02-22.

Abstract

In this work, we examined the action of two South American coralsnake (Micrurus corallinus and Micrurus dumerilii carinicauda) venoms on rat heart function in the absence and presence of treatment with Brazilian coralsnake antivenom (CAV) and varespladib (VPL), a potent phospholipase A(2) inhibitor. Anesthetized male Wistar rats were injected with saline (control) or a single dose of venom (1.5 mg/kg, i.m.) and monitored for alterations in echocardiographic parameters, serum CK-MB levels and cardiac histomorphology, the latter using a combination of fractal dimension and histopathological methods. Neither of the venoms caused cardiac functional alterations 2 h after venom injection; however, M. corallinus venom caused tachycardia 2 h after venom injection, with CAV (given i.p. at an antivenom:venom ratio of 1:1.5, v/w), VPL (0.5 mg/kg, i.p.) and CAV + VPL preventing this increase. Both venoms increased the cardiac lesional score and serum CK-MB levels compared to saline-treated rats, but only the combination of CAV + VPL prevented these alterations, although VPL alone was able to attenuate the increase in CK-MB caused by M. corallinus venom. Micrurus corallinus venom increased the heart fractal dimension measurement, but none of the treatments prevented this alteration. In conclusion, M. corallinus and M. d. carinicauda venoms caused no major cardiac functional alterations at the dose tested, although M. corallinus venom caused transient tachycardia. Both venoms caused some cardiac morphological damage, as indicated by histomorphological analyses and the increase in circulating CK-MB levels. These alterations were consistently attenuated by a combination of CAV and VPL. (AU)

• FAPESP's process: 16/11344-0 - Cardiac remodeling in rats with right heart dysfunction subjected to preventive physical training: morphofunctional and molecular study.
• Grantee: Francis Lopes Pacagnelli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/14191-6 - Potential action of the phospholipase A2 inhibitor varespladib (LY-315920) on the systemic aspects of the envenomation by Micrurus corallinus coralsnake in rats
• Grantee: Matheus Zanutto Gaspar
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 20/04287-6 - Structural and pharmacological characterization of toxins isolated from Bothrops bilineatus smaragdinus (forest viper) venom with potential modulatory activity of the motor synaptic release and cardiovascular functions
• Grantee: Rafael Stuani Floriano
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants