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Biochemical characterization and assessment of leishmanicidal effects of a new L-amino acid oxidase from Crotalus durissus collilineatus snake venom (CollinLA AO-I)

2023; Elsevier BV; Volume: 230; Linguagem: Inglês

10.1016/j.toxicon.2023.107156

1879-3150

Vitor de Freitas, Tássia R. Costa, Amanda Rodrigues Nogueira, Lorena Polloni, Thales Alves de Melo Fernandes, Lucas Ian Veloso Correia, Bruna Cristina Borges, Samuel Cota Teixeira, Marcelo José Barbosa Silva, Fernanda Gobbi Amorim, Loïc Quinton, André Lopes Saraiva, Foued Salmen Espíndola, Leo Kei Iwai, Renata Santos Rodrigues, Kelly Aparecida Geraldo Yoneyama, Veridiana de Melo Rodrigues,

Insect and Pesticide Research

This study reports the isolation of CollinLAAO-I, a new L-amino acid oxidase from Crotalus durissus collilineatus snake venom, its biochemical characterization and leishmanicidal potential in Leishmania spp. CollinLAAO-I (63.1 kDa) was successfully isolated with high purity using two chromatographic steps and represents 2.5% of total venom proteins. CollinLAAO-I displayed high enzymatic activity (4262.83 U/mg/min), significantly reducing after 28 days. The enzymatic activity of CollinLAAO-I revealed higher affinity for hydrophobic amino acids such as L-leucine, high enzymatic activity in a wide pH range (6.0–10.0), at temperatures from 0 to 25 °C, and showed complete inhibition in the presence of Na+ and K+. Cytotoxicity assays revealed IC50 of 18.49 and 11.66 μg/mL for Leishmania (L.) amazonensis and Leishmania (L.) infantum, respectively, and the cytotoxicity was completely suppressed by catalase. CollinLAAO-I significantly increased the intracellular concentration of reactive oxygen species (ROS) and reduced the mitochondrial potential of both Leishmania species. Furthermore, CollinLAAO-I decreased the parasite capacity to infect macrophages by around 70%, indicating that even subtoxic concentrations of CollinLAAO-I can interfere with Leishmania vital processes. Thus, the results obtained for CollinLAAO-I provide important support for developing therapeutic strategies against leishmaniasis.