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Novel mechanisms of pathogenesis of Sepsis and Bothrops envenomation: potential of rutin as a therapeutic agent

Grant number: 18/26015-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2019
Effective date (End): March 31, 2022
Field of knowledge:Biological Sciences - Pharmacology - Toxicology
Principal Investigator:Marcelo Larami Santoro
Grantee:Ana Teresa Azevedo Sachetto
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil


Bites by Bothrops snakes, which induce disturbances that lead to mortality or morbidity of patients, are a major public health issue in Brazil. Envenomation by Bothrops jararaca snakes induces hemostatic alterations, such as thrombocytopenia, consumptive coagulopathy, and bleedings. Furthermore, it also produces a state of local and systemic inflammatory reaction, leading to activation of pro-inflammatory cells, and release of cytokines and reactive oxygen/nitrogen species. However, no study has addressed the cross-talk between blood coagulation and inflammation, and how it influences the development of clinical events. Although Sepsis has a different pathogenic mechanism from snake envenomation, it also disturbs both coagulation and inflammation, and due to its high prevalence, the pathophysiological mechanisms of Sepsis have been better clarified. However, in common with both conditions, no totally effective therapy is available to treat complications from them, and the search for novel therapeutic targets is necessary. Rutin - a natural, safe, inexpensive, and easily available drug - shows a broad range of beneficial activities, such as antioxidant, anti-inflammatory and pro-hemostatic ones. Rutin has already been shown to be effective against the disturbances evoked by Bothrops envenomation and Sepsis. On that account, this study aims to comparatively investigate in experimental models: (a) the pathogenesis of the inflammation-coagulation alterations of Sepsis and Bothrops envenomation induced by the administration of LPS and B. jararaca venom, respectively; (b) and the therapeutic properties and the mechanism of action of rutin, regarding the disturbances evoked by administration of B. jararaca venom or LPS. We expect that the results obtained will shed new light on the pathogenesis of Bothrops envenomation and be important to diminish secondary complications not treated by antivenom therapy. (AU)

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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)
DE OLIVEIRA, NATACHA FERREIRA; AZEVEDO SACHETTO, ANA TERESA; SANTORO, MARCELO LARAMI. Two-Dimensional Blue Native/SDS Polyacrylamide Gel Electrophoresis for Analysis of Brazilian Bothrops Snake Venoms. TOXINS, v. 14, n. 10, p. 19-pg., . (13/25177-0, 18/26015-8)
AZEVEDO SACHETTO, ANA TERESA; JENSEN, JOSE RICARDO; SANTORO, MARCELO LARAMI. Liver gene regulation of hemostasis-related factors is altered by experimental snake envenomation in mice. PLoS Neglected Tropical Diseases, v. 14, n. 6, . (18/26015-8, 13/25177-0)
THOMAZINI, CAMILA MARTOS; SACHETTO, ANA TERESA AZEVEDO; DE ALBUQUERQUE, CYNTHIA ZACCANINI; DE MOURA MATTARAIA, VANIA GOMES; DE OLIVEIRA, ANA KARINA; SERRANO, SOLANGE MARIA DE TOLEDO; LEBRUN, IVO; BARBARO, KATIA CRISTINA; SANTORO, MARCELO LARAMI. Involvement of von Willebrand factor and botrocetin in the thrombocytopenia induced by Bothrops jararaca snake venom. PLoS Neglected Tropical Diseases, v. 15, n. 9, . (13/07467-1, 18/26015-8, 13/20239-8, 19/07618-6, 13/25177-0)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SACHETTO, Ana Teresa Azevedo. Novel mechanisms of the pathogenesis of sepsis and Bothrops envenomations: potential of rutin and rutin succinate as therapeutic agents. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.

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