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Synergism of in vitro plasmodicidal activity of phospholipase A2 isoforms isolated from panamanian Bothrops asper venom.
- Source :
-
Chemico-biological interactions [Chem Biol Interact] 2021 Sep 01; Vol. 346, pp. 109581. Date of Electronic Publication: 2021 Jul 21. - Publication Year :
- 2021
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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 <subscript>2</subscript> (PLA <subscript>2</subscript> 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 PLA <subscript>2</subscript> 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 PLA <subscript>2</subscript> 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 PLA <subscript>2</subscript> 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 The findings indicated the isolation of five unpublished isoforms, four Asp49-PLA, corresponding to the group of acidic isoforms, and one Lys49-PLA <subscript>2</subscript> -like. Acidic PLA <subscript>2</subscript> s catalyzed the degradation of all substrates evaluated; however, for the basic PLA <subscript>2</subscript> s, there was a preference for phosphatidylglycerol and phosphatidic acid. The antiparasitic potential of the toxins was evaluated, and the acidic PLA <subscript>2</subscript> s demonstrated action against the epimastigote forms of T. cruzi and promastigote forms of L. infantum, while the basic PLA <subscript>2</subscript> 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-PLA <subscript>2</subscript> and Lys49-PLA <subscript>2</subscript> were associated with one another, denoting synergistic action between these PLA <subscript>2</subscript> isoforms. These findings correspond to the first report of synergistic antiplasmodial action for svPLA <subscript>2</subscript> s, demonstrating that these molecules may be important targets in the search for new antiparasitic agents.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7786
- Volume :
- 346
- Database :
- MEDLINE
- Journal :
- Chemico-biological interactions
- Publication Type :
- Academic Journal
- Accession number :
- 34302801
- Full Text :
- https://doi.org/10.1016/j.cbi.2021.109581