Participation of the hepatocyte growth fator pathway in the pathophysiology of experimental envenomation of rats by Bothrops jararaca and Crotalus durissus terrificus venoms

• Grant number: 16/00211-0
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2016
• End date: January 31, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Benedito Carlos Prezoto
• Grantee: Benedito Carlos Prezoto
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Ida Sigueko Sano Martins ; Sandra Coccuzzo Sampaio Vessoni

Abstract

Crotalic and bothropic accidental envenomation processes induce to some undesirable collateral manifestations relatively resistant to conventional therapy with antivenoms. For example, local, liver and kidney injuries represent high risk of mortality or disabilities for patients. The hepatocyte growth factor activator (HGFA) and its substrate HGF are the main constituents of a cascade present in mammalian plasma that interact, structural and functionally, with coagulation and fibrinolytic systems. The HGF pathway is implicated in the pathogenesis of several diseases. During processes of tissue injuries, plasma and tissue concentrations of HGF are significantly increased. Treatment of several processes of organ injuries with reposition with HGF have been tried, with encouraging results. Our objective is to measure concentrations of HGF in plasma and liver samples of rats experimentally envenomed with Crotalus durissus terrificus and Bothrops jararaca venoms. This study would shed new light on some aspects of the pathophysiological mechanisms induced by these venoms in the blood clotting system and organ injuries. Additionally, our results can contribute for searching non-toxic peptides in these venoms with therapeutic potential and anti-inflammatory or anti-neoplastic profiles, such as activators or inhibitors of: (a) pro-HGFA or pro-HGF molecules, (b) the c-MET receptor or (c) intracellular molecular pathways related to this growth factor. (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)

PREZOTO, B. C.; KATO, E. E.; GONCALVES, L. R. C.; SAMPAIO, S. C.; SANO-MARTINS, I. S.. Elevated plasma levels of hepatocyte growth factor in rats experimentally envenomated with Bothrops jararaca venom: Role of snake venom metalloproteases. Toxicon, v. 162, p. 9-14, APR 15 2019. (16/00211-0)