A comparative study on the leishmanicidal activity of the L-amino acid oxidases BjussuLAAO-II and BmooLAAO-II isolated from Brazilian Bothrops snake venoms

Int J Biol Macromol. 2021 Jan 15:167:267-278. doi: 10.1016/j.ijbiomac.2020.11.146. Epub 2020 Nov 24.

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.

Keywords: L-amino acid oxidase; Leishmaniasis; Snake venom.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antiprotozoal Agents / isolation & purification*
  • Antiprotozoal Agents / pharmacology*
  • Bothrops*
  • Brazil
  • Chromatography
  • Crotalid Venoms / enzymology*
  • Enzyme Activation
  • L-Amino Acid Oxidase / chemistry
  • L-Amino Acid Oxidase / isolation & purification*
  • L-Amino Acid Oxidase / pharmacology*
  • Leishmania / drug effects*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Parasitic Sensitivity Tests
  • Reactive Oxygen Species / metabolism

Substances

  • Antiprotozoal Agents
  • Crotalid Venoms
  • Reactive Oxygen Species
  • L-Amino Acid Oxidase