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(Reference retrieved automatically from SciELO through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Role of crotoxin in coagulation: novel insights into anticoagulant mechanisms and impairment of inflammation-induced coagulation

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Author(s):
Bruna Terada Gimenez [1] ; Gabriel Neves Cezarette [2] ; Aline de Sousa Bomfim [3] ; Wuelton Marcelo Monteiro ; Elisa Maria de Sousa Russo ; Fabiani Gai Frantz [6] ; Suely Vilela Sampaio [7] ; Marco Aurelio Sartim
Total Authors: 8
Affiliation:
[1] University of São Paulo. School of Pharmaceutical Sciences of Ribeirão Preto. Department of Clinical Analysis, Toxicology and Food Science - Brasil
[2] University of São Paulo. School of Pharmaceutical Sciences of Ribeirão Preto. Department of Clinical Analysis, Toxicology and Food Science - Brasil
[3] University of São Paulo. Center for Cell-Based Therapy and Regional Blood Center of Ribeirão Preto - Brasil
[6] University of São Paulo. School of Pharmaceutical Sciences of Ribeirão Preto. Department of Clinical Analysis, Toxicology and Food Science - Brasil
[7] University of São Paulo. School of Pharmaceutical Sciences of Ribeirão Preto. Department of Clinical Analysis, Toxicology and Food Science - Brasil
Total Affiliations: 8
Document type: Journal article
Source: Journal of Venomous Animals and Toxins including Tropical Diseases; v. 26, 2020-11-27.
Abstract

Abstract Background: Snake venom phospholipases A2 (svPLA2) are biologically active toxins, capable of triggering and modulating a wide range of biological functions. Among the svPLA2s, crotoxin (CTX) has been in the spotlight of bioprospecting research due to its role in modulating immune response and hemostasis. In the present study, novel anticoagulant mechanisms of CTX, and the modulation of inflammation-induced coagulation were investigated. Methods: CTX anticoagulant activity was evaluated using platelet poor plasma (PPP) and whole blood (WB), and also using isolated coagulation factors and complexes. The toxin modulation of procoagulant and pro-inflammatory effects was evaluated using the expression of tissue factor (TF) and cytokines in lipopolysaccharide (LPS)-treated peripheral blood mononuclear cells (PBMC) and in WB. Results: The results showed that CTX impaired clot formation in both PPP and WB, and was responsible for the inhibition of both intrinsic (TF/factor VIIa) and extrinsic (factor IXa/factor VIIIa) tenase complexes, but not for factor Xa and thrombin alone. In addition, the PLA2 mitigated the prothrombinase complex by modulating the coagulation phospholipid role in the complex. In regards to the inflammation-coagulation cross talk, the toxin was capable of reducing the production of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, and was followed by decreased levels of TF and procoagulant activity from LPS-treated PBMC either isolated or in WB. Conclusion: The results obtained in the present study recognize the toxin as a novel medicinal candidate to be applied in inflammatory diseases with coagulation disorders. (AU)

FAPESP's process: 16/04079-9 - Anti-inflammatory potential evaluation of crotoxin, a phospholipase A2 isolated from the venom of Crotalus durissus terrificus, in endotoxemia model
Grantee:Gabriel Neves Cezarette
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis
Grantee:Suely Vilela
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 15/06290-6 - Evaluation of anti-inflammatory potential of crotoxin, a phospholipase A2 isolated from Crotalus durissus terrificus venom, in a disseminated intravascular coagulation model induced by endotoxemia
Grantee:Marco Aurélio Sartim
Support Opportunities: Scholarships in Brazil - Post-Doctoral