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Contribution of local injury evoked by Bothrops jararaca snake venom to the genesis of systemic hemostatic disturbances

Grant number: 10/08162-1
Support type:Regular Research Grants
Duration: December 01, 2010 - November 30, 2012
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Marcelo Larami Santoro
Grantee:Marcelo Larami Santoro
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated grant(s):10/52559-3 - Importance of local damage induced by snake venom metalloproteinases in the induction of thrombocytopenia in envenomations, AP.R


Bothrops jararaca snake venom evokes various clinical manifestations in envenomed people, which have been classified as local or systemic, depending on the proximity in relation to the site of the bite. Among the systemic manifestations of envenomation, hemostatic disturbances are the most prevalent; among local manifestations, inflammatory reaction and their complications are the most conspicuous. The pathophysiology of hemostatic disturbances is known to be complex in Bothrops sp. envenomation, and that several mechanisms may contribute to the manifestation of bleeding tendencies. Taking into account that thrombocytopenia is one of the most frequent hemostatic disturbances in victims, the main goal of this proposal is to investigate the pathophysiological mechanisms that induce hemostatic disturbances, especially thrombocytopenia, in accidents inflicted by B. jararaca snakes. It is imperative to known the causes of thrombocytopenia in these accidents, since it is a useful prognostic factor to detect the development of local and systemic complications, inasmuch as it is positively associated with the development of bleeding and with the severity of envenomation. Thus, an experimental envenomation model will be used to evaluate: (a) the importance of local injury to evoke hemostatic disturbances and (b) which protein families found in B. jararaca venom elicit thrombocytopenia in vivo. (AU)

Scientific publications (7)
(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)
PREZOTTO-NETO, JOSE P.; KIMURA, LOUISE F.; ALVES, ANDRE F.; MARIA GUTIERREZ, JOSE; OTERO, RAFAEL; SUAREZ, ANA M.; SANTORO, MARCELO L.; BARBARO, KATIA C. Biochemical and biological characterization of Bothriechis schlegelii snake venoms from Colombia and Costa Rica. Experimental Biology and Medicine, v. 241, n. 18, p. 2075-2085, DEC 2016. Web of Science Citations: 4.
ELISA PEICHOTO, MARIA; SANTORO, MARCELO LARAMI. Patagonfibrase modifies protein expression of tissue factor and protein disulfide isomerase in rat skin. Toxicon, v. 119, p. 330-335, SEP 1 2016. Web of Science Citations: 4.
SANTORO, MARCELO LARAMI; DO CARMO, THAIS; LOPES CUNHA, BRUNA HELOISA; ALVES, ANDRE FONSECA; ZELANIS, ANDRE; DE TOLEDO SERRANO, SOLANGE MARIA; GREGO, KATHLEEN FERNANDES; SANT'ANNA, SAVIO STEFANINI; BARBARO, KATIA CRISTINA; FERNANDES, WILSON. Ontogenetic Variation in Biological Activities of Venoms from Hybrids between Bothrops erythromelas and Bothrops neuwiedi Snakes. PLoS One, v. 10, n. 12 DEC 29 2015. Web of Science Citations: 5.
SENISE, LUANA V.; YAMASHITA, KARINE M.; SANTORO, MARCELO L. Bothrops jararaca envenomation: Pathogenesis of hemostatic disturbances and intravascular hemolysis. Experimental Biology and Medicine, v. 240, n. 11, p. 1528-1536, NOV 2015. Web of Science Citations: 10.
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: 21.
PEICHOTO, MARIA E.; TAVARES, FLAVIO L.; SANTORO, MARCELO L.; MACKESSY, STEPHEN P. Venom proteomes of South and North American opisthoglyphous (Colubridae and Dipsadidae) snake species: A preliminary approach to understanding their biological roles. Comparative Biochemistry and Physiology D-Genomics & Proteomics, v. 7, n. 4, p. 361-369, DEC 2012. Web of Science Citations: 26.
ELISA PEICHOTO, MARIA; ZYCHAR, BIANCA CESTARI; LUIZ TAVARES, FLAVIO; GONCALVES, LUIS ROBERTO CAMARGO; ACOSTA, OFELIA; SANTORO, MARCELO LARAMI. Inflammatory effects of patagonfibrase, a metalloproteinase from Philodryas patagoniensis (Patagonia Green Racer; Dipsadidae) venom. Experimental Biology and Medicine, v. 236, n. 10, p. 1166-1172, OCT 2011. Web of Science Citations: 10.

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