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Involvement of Von Willebrand factor in hemostatic disturbances induced by Bothrops jararaca snake venom: experimental study

Grant number: 13/25177-0
Support Opportunities:Regular Research Grants
Duration: January 01, 2015 - December 31, 2017
Field of knowledge:Biological Sciences - Pharmacology - Toxicology
Principal Investigator:Marcelo Larami Santoro
Grantee:Marcelo Larami Santoro
Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Associated researchers:José Ricardo Jensen ; Katia Cristina Barbaro Nogueira ; Vânia Gomes de Moura Mattaraia
Associated grant(s):16/50411-5 - Isolation and characterization of Brothrops jararaca snake venom proteins that induce thrombocytopenia, AP.R SPRINT


Bothrops jararaca snake venom disrupts various biological systems in a complex and dynamic manner, causing thereby the rapid death of natural preys. Among these biological systems, the hemostatic system is a crucial target for snake venoms; particularly, B. jararaca venom has various pro- and anti-hemostatic activities. Given the wide range of hemostatic activities found in this venom, bleeding disorders occurring in patients are multifactorial. However, it is intriguing that some important features of hemorrhagic manifestations presented by patients bitten by B. jararaca, e.g. gingival bleeding, epistaxis, petechiae and suffusions, resemble those observed in patients with von Willebrand disease. Likewise, although the venom induces thrombocytopenia in envenomed patients, it is unknown whether von Willebrand factor (vWF) is involved in such process. Thus, this project aims: (1) to analyze the occurrence of quantitative and qualitative changes of vWF and its cleavage enzyme, ADAMTS13, during experimental envenomation by B. jararaca; (2) to investigate the role of vWF in the development of venom-induced thrombocytopenia. (AU)

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Scientific publications (12)
(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)
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, . (10/08162-1, 10/52559-3, 13/25177-0)
ROSA, JAQUELINE GOMES; DE ALBUQUERQUE, CYNTHIA ZACCANINI; DE MOURA MATTARAIA, VANIA GOMES; SANTORO, MARCELO LARAMI. Comparative study of platelet aggregation and secretion induced by Bothrops jararaca snake venom and thrombin. Toxicon, v. 159, p. 50-60, . (18/07819-9, 13/25177-0)
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)
AZEVEDO SACHETTO, ANA TERESA; ROSA, JAQUELINE GOMES; SANTORO, MARCELO LARAMI. Rutin (quercetin-3-rutinoside) modulates the hemostatic disturbances and redox imbalance induced by Bothrops jararaca snake venom in mice. PLoS Neglected Tropical Diseases, v. 12, n. 10, . (13/25177-0)
MALAQUE, C. M. S.; DUAYER, I. F.; SANTORO, M. L.. Acute kidney injury induced by thrombotic microangiopathy in two cases of Bothrops envenomation. CLINICAL TOXICOLOGY, v. 57, n. 3, p. 213-216, . (13/25177-0)
SANTOS DE OLIVEIRA, PERCILLIA VICTORIA; GARCIA-ROSA, SHEILA; AZEVEDO SACHETTO, ANA TERESA; SOARES MORETTI, ANA IOCHABEL; DEBBAS, VICTOR; DE BESSA, TIPHANY CORALIE; SILVA, NATHALIA TENGUAN; PEREIRA, ALEXANDRE DA COSTA; MARTINS-DE-SOUZA, DANIEL; SANTORO, MARCELO LARAMI; et al. Protein disulfide isomerase plasma levels in healthy humans reveal proteomic signatures involved in contrasting endothelial phenotypes. REDOX BIOLOGY, v. 22, . (17/25588-1, 18/07511-4, 17/19866-9, 14/20595-1, 13/08711-3, 13/25177-0, 14/10068-4, 13/07937-8)
AGUSTINA QUINTANA, MARIA; SCIANI, JULIANA MOZER; VATTI AUADA, ALINE VIVIAN; MERCEDES MARTINEZ, MARIA; NICOLAS SANCHEZ, MAGAS; SANTORO, MARCELO LARAMI; FAN, HUI WEN; ELISA PEICHOTO, MARIA. Stinging caterpillars from the genera Podalia, Leucanella and Lonomia in Misiones, Argentina: A preliminary comparative approach to understand their toxicity. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, v. 202, p. 55-62, . (13/25177-0)
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, . (13/07467-1, 10/08162-1, 13/13548-4, 08/02996-8, 09/15413-3, 13/25177-0)
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)
THOMAZINI, CAMILA MARTOS; SILVA SOARES, ROSANGELA DE PAULA; FLORES DA ROCHA, TANIA RUBIA; AZEVEDO SACHETTO, ANA TERESA; SANTORO, MARCELO LARAMI. Optimization of von Willebrand factor multimer analysis in vertical mini-gel electrophoresis systems: A rapid procedure. THROMBOSIS RESEARCH, v. 175, p. 76-83, . (13/20239-8, 13/25177-0)
RODRIGUES, MARIANA VALOTTA; DE CASTRO, SIMONE OLIVEIRA; DE ALBUQUERQUE, CYNTHIA ZACCANINI; DE MOURA MATTARAIA, VANIA GOMES; SANTORO, MARCELO LARAMI. The gingival vein as a minimally traumatic site for multiple blood sampling in guinea pigs and hamsters. PLoS One, v. 12, n. 5, . (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)

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