1. A comparative study on the leishmanicidal activity of the L-amino acid oxidases BjussuLAAO-II and BmooLAAO-II isolated from Brazilian Bothrops snake venoms.
- Author
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Barbosa LG, Costa TR, Borges IP, Costa MS, Carneiro AC, Borges BC, Silva MJB, Amorim FG, Quinton L, Yoneyama KAG, de Melo Rodrigues V, Sampaio SV, and Rodrigues RS
- Subjects
- Amino Acid Sequence, Animals, Brazil, Chromatography, Enzyme Activation, L-Amino Acid Oxidase chemistry, Membrane Potential, Mitochondrial drug effects, Mitochondria drug effects, Mitochondria genetics, Mitochondria metabolism, Parasitic Sensitivity Tests, Reactive Oxygen Species metabolism, Antiprotozoal Agents isolation & purification, Antiprotozoal Agents pharmacology, Bothrops, Crotalid Venoms enzymology, L-Amino Acid Oxidase isolation & purification, L-Amino Acid Oxidase pharmacology, Leishmania drug effects
- Abstract
This study aims to examine whether two L-amino acid oxidases isolated from Bothrops snake venom (SV-LAAOs) were cytotoxic to Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis, two causative agents of leishmaniasis, which is an endemic disease in tropical and subtropical countries. The SV-LAAOs BjussuLAAO-II and BmooLAAO-II were isolated from Bothrops jararacussu and Bothrops moojeni venom, respectively, through a three-step chromatography process that used molecular exclusion, hydrophobic interaction, and affinity columns. BmooLAAO-II is a new SV-LAAO isoform that we isolated in this study. The purified BjussuLAAO-II and BmooLAAO-II had high L-amino acid oxidase-specific activity: 3481.17 and 4924.77 U/mg/min, respectively. Both SV-LAAOs were strongly cytotoxic to the two Leishmania species, even at low concentrations. At the same concentration, BjussuLAAO-II and BmooLAAO-II exerted different cytotoxic effects on the parasites. We reported for the first time that the SV-LAAOs suppressed cell proliferation and altered the mitochondrial membrane potential of the two Leishmania species. Surprisingly, BjussuLAAO-II increased the intracellular reactive oxygen species production only in L. (L.) amazonensis, while BmooLAAO-II increased the intracellular reactive oxygen species production only in L. (V.) braziliensis, indicating that these SV-LAAOs had a certain specificity of action., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2021
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