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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 - April 30, 2021
Field of knowledge:Biological Sciences - 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)