Synergistic effect of serine protease inhibitors and a bothropic antivenom in reducing local hemorrhage and coagulopathy caused by Bothrops jararaca venom

Author(s)

Silva, G. M. ^[1] ; Berto, D. H. ^[1] ; Lima, C. A. ^[1] ; Waitman, K. B. ^[1] ; Lima, C. F. G. ^[1] ; Prezoto, B. C. ^[2] ; Vieira, M. L. ^[3] ; Rocha, M. M. T. ^[4] ; Goncalves, L. R. C. ^[5] ; Andrade, S. A. ^[1]

Affiliation

^[1] Butantan Inst, Lab Pain & Signaling, Sao Paulo - Brazil

^[2] Butantan Inst, Lab Pharmacol, Sao Paulo - Brazil

^[3] Fed Univ Minas Gerais UFMG, Dept Microbiol, Belo Horizonte, MG - Brazil

^[4] Butantan Inst, Lab Herpetol, Sao Paulo - Brazil

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

• Document type: Journal article
• Source: Toxicon; v. 199, p. 87-93, AUG 2021.
• Web of Science Citations: 0

Abstract

Snakebite accidents are a public health problem that affects the whole world, causing thousands of deaths and amputations each year. In Brazil, snakebite envenomations are caused mostly by snakes from the Bothrops genus. The local symptoms are characterized by pain, swelling, ecchymosis, and hemorrhages. Systemic disturbances can lead to necrosis and amputations. The present treatment consists of intravenous administration of bothropic antivenom, which is capable of reversing most of the systemic symptoms, while presenting limitations to treat the local effects, such as hemorrhage and to neutralize the snake venom serine protease (SVSP). In this context, we aimed to evaluate the activity of selective serine protease inhibitors (pepC and pepB) in combination with the bothropic antivenom in vivo. Further, we assessed their possible synergistic effect in the treatment of coagulopathy and hemorrhage induced by Bothrops jararaca venom. For this, we evaluated the in vivo activity in mouse models of local hemorrhage and a series of in vitro hemostasis assays. Our results showed that pepC and pepB, when combinated with the antivenom, increase its protective activity in vivo and decrease the hemostatic disturbances in vitro with high selectivity, possibly by inhibiting botropic proteases. These data suggest that the addition of serine protease inhibitor to the antivenom can improve its overall potential. (AU)

• FAPESP's process: 17/00236-5 - Platelets at the interface of immunity, inflammation and hemostasis modulation in leptospirosis
• Grantee: Mônica Larucci Vieira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/04321-7 - Synthesis of peptidic inhibitors: a strategy for improvement of the antibothrops serum produced by the Butantan Institute
• Grantee: Sonia Aparecida de Andrade Chudzinski
• Support Opportunities: Regular Research Grants