1. Synergism of in vitro plasmodicidal activity of phospholipase A2 isoforms isolated from panamanian Bothrops asper venom.
- Author
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Simões-Silva R, Alfonso JJ, Gómez AF, Sobrinho JC, Kayano AM, de Medeiros DSS, Teles CBG, Quintero A, Fuly AL, Gómez CV, Pereira SS, da Silva SL, Stábeli RG, and Soares AM
- Subjects
- Amino Acid Sequence, Animals, Antiprotozoal Agents chemistry, Antiprotozoal Agents isolation & purification, Bothrops metabolism, Drug Synergism, Isoelectric Point, Leishmania infantum drug effects, Panama, Parasitic Sensitivity Tests, Phospholipases A2 isolation & purification, Phospholipases A2 pharmacology, Protein Isoforms chemistry, Protein Isoforms isolation & purification, Protein Isoforms pharmacology, Sequence Alignment, Antiprotozoal Agents pharmacology, Phospholipases A2 chemistry, Plasmodium falciparum drug effects, Snake Venoms metabolism
- Abstract
Bothrops asper is one of the most important snake species in Central America, mainly because of its medical importance in countries like Ecuador, Panama and Costa Rica, where this species causes a high number of snakebite accidents. Several basic phospholipases A
2 (PLA2 s) have been previously characterized from B. asper venom, but few studies have been carried out with its acidic isoforms. In addition, since snake venom is a rich source of bioactive substances, it is necessary to investigate the biotechnological potential of its components. In this context, this study aimed to carry out the biochemical characterization of PLA2 isoforms isolated from B. asper venom and to evaluate the antiparasitic potential of these toxins. The venom and key fractions were subjected to different chromatographic steps, obtaining nine PLA2 s, four acidic ones (BaspAc-I, BaspAc-II, BaspAc-III and BaspAc-IV) and five basic ones (BaspB-I, BaspB-II, BaspB-III, BaspB-IV and BaspB-V). The isoelectric points of the acidic PLA2 s were also determined, which presented values ranging between 4.5 and 5. The findings indicated the isolation of five unpublished isoforms, four Asp49-PLA, corresponding to the group of acidic isoforms, and one Lys49-PLA2 -like. Acidic PLA2 s catalyzed the degradation of all substrates evaluated; however, for the basic PLA2 s, there was a preference for phosphatidylglycerol and phosphatidic acid. The antiparasitic potential of the toxins was evaluated, and the acidic PLA2 s demonstrated action against the epimastigote forms of T. cruzi and promastigote forms of L. infantum, while the basic PLA2 s BaspB-II and BaspB-IV showed activity against P. falciparum. The results indicated an increase of up to 10 times in antiplasmodial activity, when the Asp49-PLA2 and Lys49-PLA2 were associated with one another, denoting synergistic action between these PLA2 isoforms. These findings correspond to the first report of synergistic antiplasmodial action for svPLA2 s, demonstrating that these molecules may be important targets in the search for new antiparasitic agents., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
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