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Phospholipase A2 inhibitors (PLIs) present in venomous and non-venomous snake plasmas and evaluation of the neutralizing activity of these inhibitors on the phospholipase A2 (PLA2) activities of snake venoms

Grant number: 18/25786-0
Support type:Regular Research Grants
Duration: May 01, 2019 - July 31, 2021
Field of knowledge:Biological Sciences - Physiology - Compared Physiology
Principal Investigator:Anita Mitico Tanaka-Azevedo
Grantee:Anita Mitico Tanaka-Azevedo
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Assoc. researchers:Alexandre Keiji Tashima ; Aparecida Sadae Tanaka ; Benedito Carlos Prezoto ; Karen de Morais Zani ; Kathleen Fernandes Grego

Abstract

There is a great diversity of venomous and non-venomous snakes in Brazil and in the world. The biological and behavioral differences of these two groups have been increasingly studied. Venomous snakes are responsible for 5 million human accidents per year, a fact that encourages knowledge about all aspects of envenomation. Nowadays, it is known that 90% of the venom of these snakes is composed of about 15 families of proteins that trigger the systemic and local effects of envenomation. The use of serum therapy in this treatment has been efficient in minimizing the systemic effects, however, the difficult access to adequate serum and the rapid action of some families of proteins (mainly metalloproteases and phospholipases A2) developed by local symptoms are not totally neutralized, leading to around 400 thousand amputations per year. So, the study of proteins present in the blood of animals has been one of the alternatives found for the development of new drugs, which can contribute in the neutralization of these effects. Inhibitors of phospholipases A2 (PLI) have been one of the major targets of these studies, for the ability to neutralize many effects of different classes of PLA2, including human ones. The presence of these PLIs in different animals (venomous snakes, non-venomous snakes and mammals) has also stimulated the interest by their biological role as well as their mechanism of action.Thus, in recent years, our group has been studying venom and plasma proteins from snakes. We have recently isolated a serum ³-type PLI from the venomous snake Bothrops jararaca (B. jararaca) plasma and, we have also elucidated some characteristics of its structure and inhibitory action of the enzymatic, edematogenic and myionecrotic activity of PLA2. Thus, the isolation of a PLI of Boa constrictor, a non-venomous snake, the comparison of this inhibitor with B. jararaca plasma PLI, as well as the elucidation of the mechanism of action of both inhibitors in the envenomation and inflammatory processes, will contribute for the development of new alternatives that complement the treatment of ophidian accidents, besides contributing to the elucidation of the physiological role of these proteins in these animals. (AU)

Scientific publications (8)
(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)
AGUIAR, WESLEI DA SILVA; GALIZIO, NATHALIA DA COSTA; SANT'ANNA, SAVIO STEFANINI; SILVEIRA, GIOVANNI PEREZ M.; RODRIGUES, FABIOLA DE SOUZA; GREGO, KATHLEEN FERNANDES; DE MORAIS-ZANI, KAREN; TANAKA-AZEVEDO, ANITA MITICO. Ontogenetic study of Bothrops jararacussu venom composition reveals distinct profiles. Toxicon, v. 186, p. 67-77, OCT 30 2020. Web of Science Citations: 0.
TASIMA, LIDIA J.; HATAKEYAMA, DANIELA M.; SERINO-SILVA, CAROLINE; RODRIGUES, CAROLINE F. B.; DE LIMA, V, EDUARDO O.; SANT'ANNA, SAVIO S.; GREGO, KATHLEEN F.; DE MORAIS-ZANI, KAREN; SANZ, LIBIA; CALVETE, JUAN J.; TANAKA-AZEVEDO, ANITA M. Comparative proteomic profiling and functional characterization of venom pooled from captive Crotalus durissus terrificus specimens and the Brazilian crotalic reference venom. Toxicon, v. 185, p. 26-35, OCT 15 2020. Web of Science Citations: 0.
HATAKEYAMA, DANIELA MIKI; TASIMA, LIDIA JORGE; BRAVO-TOBAR, CESAR ADOLFO; SERINO-SILVA, CAROLINE; TASHIMA, ALEXANDRE KEIJI; BITTENCOURT RODRIGUES, CAROLINE FABRI; AGUIAR, WESLEI DA SILVA; GALIZIO, NATHALIA DA COSTA; VENANCIO DE LIMA, EDUARDO OLIVEIRA; KAVAZOI, VICTOR KOITI; GUTIERREZ-MARIN, JUAN DAVID; DE FARIAS, IASMIM BAPTISTA; SANT'ANNA, SAVIO STEFANINI; GREGO, KATHLEEN FERNANDES; DE MORAIS-ZANI, KAREN; TANAKA-AZEVEDO, ANITA MITICO. Venom complexity of Bothrops atrox (common lancehead) siblings. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, OCT 12 2020. Web of Science Citations: 0.
MACHADO BRAGA, JACQUELINE RAMOS; DE MORAIS-ZANI, KAREN; PEREIRA, DIEGO DOS SANTOS; SANT'ANNA, SAVIO STEFANINI; GALIZIO, NATHALIA DA COSTA; TANAKA-AZEVEDO, ANITA MITICO; GOMES VILARINHO, ARIEL RODRIGUES; RODRIGUES, JOSE LUCCA; TEIXEIRA DA ROCHA, MARISA MARIA. Sexual and ontogenetic variation of Bothrops leucurus venom. Toxicon, v. 184, p. 127-135, SEP 2020. Web of Science Citations: 0.
BITTENCOURT RODRIGUES, CAROLINE FABRI; SERINO-SILVA, CAROLINE; DE MORAIS-ZANI, KAREN; KAVAZOI, VICTOR KOITI; NOGUEIRA CARVALHO, MARCELO PIRES; GREGO, KATHLEEN FERNANDES; CHIARELLI, TASSIA; TASHIMA, ALEXANDRE KEIJI; TOYAMA, MARCOS HIKARI; TANAKA-AZEVEDO, ANITA MITICO. Boa.PLI: Structural and functional characterization of the gamma phospholipase A2 plasma inhibitor from the non-venomous Brazilian snake Boa constrictor. PLoS One, v. 15, n. 2 FEB 27 2020. Web of Science Citations: 0.
ADRIANA SIMIZO; EDUARDO S. KITANO; SÁVIO S. SANT’ANNA; KATHLEEN FERNANDES GREGO; ANITA MITICO TANAKA-AZEVEDO; ALEXANDRE K. TASHIMA. Comparative gender peptidomics of Bothrops atrox venoms: are there differences between them?. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, p. -, 2020. Web of Science Citations: 0.
LEANDRO NORBERTO DA SILVA-JÚNIOR; LARA DE SOUZA ABREU; CAROLINE FABRI BITTENCOURT RODRIGUES; NATHÁLIA DA COSTA GALIZIO; WESLEI DA SILVA AGUIAR; CAROLINE SERINO-SILVA; VALDOMIRO SOUZA DOS SANTOS; ISABELLA ALVES COSTA; LUIS VICENTE FRANCO OLIVEIRA; SÁVIO STEFANINI SANT’ANNA; KATHLEEN FERNANDES GREGO; ANITA MITICO TANAKA-AZEVEDO; LEANDRO NASCIMENTO DA SILVA RODRIGUES; KAREN DE MORAIS-ZANI. Geographic variation of individual venom profile of Crotalus durissus snakes. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 26, p. -, 2020. Web of Science Citations: 0.
AGUIAR, WESLEI DA SILVA; GALIZIO, NATHALIA DA COSTA; SERINO-SILVA, CAROLINE; SANT'ANNA, SAVIO STEFANINI; GREGO, KATHLEEN FERNANDES; TASHIMA, ALEXANDRE KEIJI; NISHIDUKA, ERIKA SAYURI; DE MORAIS-ZANI, KAREN; TANAKA-AZEVEDO, ANITA MITICO. Comparative compositional and functional analyses of Bothrops moojeni specimens reveal several individual variations. PLoS One, v. 14, n. 9 SEP 12 2019. Web of Science Citations: 0.

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