Anti-inflammatory potential evaluation of crotoxin, a phospholipase A2 isolated from the venom of Crotalus durissus terrificus, in endotoxemia model

• Grant number: 16/04079-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2016
• End date: January 31, 2019
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Suely Vilela
• Grantee: Gabriel Neves Cezarette
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 11/23236-4 - Native and recombinant animal toxins: functional, structural and molecular analysis, AP.TEM

Abstract

Sepsis, or generalized infection, is a syndrome characterized by a series of serious manifestations throughout the body caused by infections, pathogens such bacterias (gram-positive or gram-negatives) and fungi. Among the main bacterial components responsible for triggering inflammation in sepsis, we can mention the lipopolysaccharide (LPS). This bacterial membrane molecule is responsible for recognition and leukocyte activation, and inducing expression of pro-inflammatory cytokines such as TNF-± and IL-1², and starting the inflammation process. The crotoxin (CTX) is a phospholipase A2 (PLA2) representing the major component in Crotalus gender snakes venoms. Recent studies have shown that CTX presents a important immunomodulatory and anti-inflammatory activity, notice in models of mouse paw edema and leukocyte migration. Considering that there are no scientific studies assessing the response of crotoxin against any pathology induced by LPS, the objective of the present work concerns to evaluate the capacity of CTX in the resolution of inflammation in endotoxemia model. The septic shock will be induced by LPS i.p. administration in mice, where crotoxin wil be administrated in different doses and times before and after the LPS administration, and the inflammation resolution wil be evaluated by the dosage of hematological parameters (white boold cells counting), coagulation parameters (prothrombin time and thromboplastin parcial activated time) and pro inflammatory cytokines. Taking into consideration the immunomodulatory agents use as therapeutic strategy for sepsis, the present work intends to introduce CTX as a novel agent capable in assist the inflammatory resolution of sepsis. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BRUNA TERADA GIMENEZ; GABRIEL NEVES CEZARETTE; ALINE DE SOUSA BOMFIM; WUELTON MARCELO MONTEIRO; ELISA MARIA DE SOUSA RUSSO; FABIANI GAI FRANTZ; SUELY VILELA SAMPAIO; MARCO AURELIO SARTIM. Role of crotoxin in coagulation: novel insights into anticoagulant mechanisms and impairment of inflammation-induced coagulation. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, 2020-11-27. (16/04079-9, 11/23236-4, 15/06290-6)

CEZARETTE, G. N.; SARTIM, M. A.; SAMPAIO, S. V.. Inflammation and coagulation crosstalk induced by BJcuL, a galactose-binding lectin isolated from Bothrops jararacussu snake venom. International Journal of Biological Macromolecules, v. 144, p. 9-pg., 2020-02-01. (11/23236-4, 15/06290-6, 16/04079-9)

CEZARETTE, G. N.; SARTIM, M. A.; SAMPAIO, S. V.. Inflammation and coagulation crosstalk induced by BJcuL, a galactose-binding lectin isolated from Bothrops jararacussu snake venom. International Journal of Biological Macromolecules, v. 144, p. 296-304, FEB 1 2020. (11/23236-4, 15/06290-6, 16/04079-9)