l-Amino acid oxidase activity present in fractions of Bothrops jararaca venom is responsible for the induction of programmed cell death in Trypanosoma cruzi

Bothrops jararaca venom induces programmed cell death in epimastigotes of Trypanosoma cruzi. Here we fractionated the venom and observed that the anti-T. cruzi activity was associated with fractions that present l-amino acid oxidase (l-AAO) activity. l-AAO produces H2O2, which is highly toxic. The addition of catalase to the medium, a H2O2 scavenger, reverted the killing capacity of venom fractions. The anti-T. cruzi activity was also abolished when parasites were cultured in a medium without hydrophobic amino acids that are essential for l-AAO activity. These results were confirmed with a commercial purified l-AAO. Treatment for 24 h with fractions that present l-AAO activity induced parasites cytoplasmic retraction, mitochondrial swelling and DNA fragmentation, all morphological characteristics of programmed cell death. Similar changes were also observed when parasites were treated with H2O2. These results indicate that H2O2, the product of l-AAO reaction, induces programmed cell death explaining the anti-T. cruzi activity of B. jararaca venom.