Pathogenesis of systemic hemostatic disturbances induced by Bothrops jararaca snake venom

• Grant number: 10/02568-6
• Support type: Scholarships in Brazil - Master
• Effective date (Start): December 01, 2010
• Effective date (End): July 31, 2012
• Field of knowledge: Biological Sciences - Pharmacology - Toxicology
• Principal researcher: Marcelo Larami Santoro
• Grantee: Karine Miki Yamashita
• Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Resumo do artigo que está sendo submetido à publicação no Journal of Thrombosis and Haemostasis, referente aos resultados obtidos pela aluna em sua dissertação de mestrado.The release of plasma tissue factor (TF) in bloodstream has never been demonstrated in snake envenomation, although it may aggravate the bleeding tendency. Aiming to investigate the contribution of venom metalloproteinases and serine proteinases, as well as TF expression, to the genesis of hemostatic disturbances in snake envenomation, crude Bothrops jararaca venom was previously incubated with specific inhibitors, and administered s.c. or i.v. into rats. Circulating venom levels increased more rapidly in the i.v. group, and incubation of venom with inhibitors failed to exert any noticeable effect on it. Platelet counts were markedly diminished in rats administered with venom in comparison with saline-treated rats, and only Na2-EDTA could minimally reverse it. However, Na2-EDTA incubation completely blocked plasma fibrinogen consumption, prolongation of prothrombin time, and hemorrhage at the site of venom inoculation. Factor VII levels were not reduced during envenomation. Envenomed rats showed a marked elevation in TF levels in plasma, as well as raised expression in TF in lung and skin tissue samples, which were also blocked by Na2-EDTA. On the other hand, protein disulfide isomerase (PDI) expression in skin was downregulated at 6 h in all groups treated with venom. These findings show that metalloproteinases are essential venom components to induce coagulopathy, local hemorrhage and the rise in plasma TF levels in rats, but neither metalloproteinases nor serine proteinases had a direct involvement in the genesis thrombocytopenia. Those data reveal that high levels of TF in plasma may occur during snake envenomation, resembling the etiopathogenesis of true disseminated intravascular coagulation syndrome. (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)

YAMASHITA, KARINE M.; ALVES, ANDRE F.; BARBARO, KATIA C.; SANTORO, MARCELO L. Bothrops jararaca Venom Metalloproteinases Are Essential for Coagulopathy and Increase Plasma Tissue Factor Levels during Envenomation. PLoS Neglected Tropical Diseases, v. 8, n. 5 MAY 2014. Web of Science Citations: 20.