Bothrops moojeni venom kills Leishmania spp. with hydrogen peroxide generated by its L-amino acid oxidase

Biochem Biophys Res Commun. 2001 Jan 26;280(3):620-4. doi: 10.1006/bbrc.2000.4175.

Abstract

Leishmaniasis is an endemic tropical disease in South America, with few therapeutic approaches. Snake venoms are complex protein mixtures with biological actions that could be used as tools for drug development. Here we show that Bothrops moojeni crude venom presented a killing effect in vitro against Leishmania spp. promastigotes, but not with amastigotes, as determined by a viability assay using the mitochondrial oxidative function. Purification of active fractions from crude venom was performed by molecular exclusion and ion exchange chromatography. Anti-Leishmania and l-amino acid oxidase (L-AAO, EC.1.4.3.2.) activities co-eluted in the same fractions. The molecular weight of the active enzyme was estimated to be 140 kDa by molecular exclusion chromatography, and 69 kDa by SDS--PAGE, with a 4.8 isoelectric point. Using substrate subtraction and catalase for scavenging, the action of L-AAO was demonstrated to be hydrogen-peroxide-dependent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / isolation & purification
  • Amino Acid Oxidoreductases / metabolism*
  • Amino Acid Oxidoreductases / pharmacology*
  • Animals
  • Antiprotozoal Agents / isolation & purification
  • Antiprotozoal Agents / pharmacology*
  • Bothrops*
  • Crotalid Venoms / chemistry
  • Crotalid Venoms / pharmacology*
  • Hydrogen Peroxide / metabolism*
  • Hydrogen Peroxide / pharmacology*
  • In Vitro Techniques
  • L-Amino Acid Oxidase
  • Leishmania / drug effects*

Substances

  • Antiprotozoal Agents
  • Crotalid Venoms
  • Hydrogen Peroxide
  • Amino Acid Oxidoreductases
  • L-Amino Acid Oxidase