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Complement system inhibition as means for controlling inflammation associated to envenomations

Grant number: 19/27348-3
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): September 01, 2020
Effective date (End): August 31, 2022
Field of knowledge:Biological Sciences - Immunology - Immunochemistry
Principal researcher:Denise Vilarinho Tambourgi
Grantee:Dayanne Carla Fernandes
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated research grant:13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID

Abstract

The complement system, one of the first lines of defense of the innate immunity, is a major mechanism by which the body recognizes foreign substances and pathogens. This system consists of over 40 proteins, among them regulators and membrane-bound receptors and plasma proteins that interact with multiple cells and mediators of the immune system. These interactions vary according to the pathophysiologic context and occur at different stages of the immune reaction. The dysregulation of the complement activation often results in acute or chronic inflammation and can contribute to the development of several diseases. Venoms from poisonous animals contain a plethora of toxic molecules including many proteolytic enzymes. These proteolytic enzymes have a range of functions in the pathology caused by the envenomation and some may aid to immobilize and/or kill the prey. In nature a wide range of animal venoms and animal secretions are found to interact with complement system, which activation can contribute to both the spread of the venom and the inflammatory response. So far, therapeutic strategies for treating accidents by poisonous animals not always reliable include antivenom, corticosteroids, vasopressors, infusion of platelets, catecholamines, hyperbaric oxygenation, etc. An in-depth characterization of the action of venoms on the activation of the complement system as well as the use of complement inhibitors in experimental models of envenomation may shed light on potentially specific therapies targeting this pathway. Thus, the aim of this project is to investigate the possible therapeutic use of complement inhibitors to prevent or reduce venoms local/systemic pathologies. (AU)

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