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Cytotoxic, apoptotic and inflammatory actions of L-amino acid oxidase from Bothrops jararaca venom in rat macrophages

Grant number: 12/50883-3
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): May 01, 2013
Effective date (End): April 30, 2015
Field of knowledge:Biological Sciences - Pharmacology - Toxicology
Principal Investigator:Stephen Hyslop
Grantee:Fabiana Vieira Fonseca
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

L-Amino acid oxidases (LAAO) are enzymes with a wide distribution among animal venoms, particularly in snakes. Various studies have shown that LAAOs exert a variety of biological activities such as the inhibition or stimulation of platelet aggregation and the induction of apoptosis and edema, in addition to antimicrobial, antiviral, antiparasite and antitumor activities. Macrophages play an important role in the local inflammatory response after envenoming by Bothrops snakes, primarily because of their ability to release cytokines and other mediators (free radicals, etc.) and their phagocytic activity that contributes to the removal of necrotic tissue. Although LAAO can cause edema and an inflammatory response involving cell migration, the effect of this enzyme on macrophages has not been studied in detail. In this project, we aim to investigate the effect of LAAO from Bothrops jararaca venom on rat macrophages in vitro and in vivo. Specifically, we will assess the cytotoxicity and apoptotic activity of LAAO and its ability to stimulate the formation of free radicals, the release of cytokines and the migration of macrophages. The results of this study should contribute to our understanding of the physiopathology of envenoming by this toxin. (AU)