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

• Published in: Toxicon (Oxford) Vol. 230; p. 107156
• Main Authors: de Freitas, Vitor, Costa, Tássia Rafaella, Nogueira, Amanda Rodrigues, Polloni, Lorena, Alves de Melo Fernandes, Thales, Correia, Lucas Ian Veloso, Borges, Bruna Cristina, Teixeira, Samuel Cota, Silva, Marcelo José Barbosa, Amorim, Fernanda Gobbi, Quinton, Loïc, Saraiva, André Lopes, Espindola, Foued Salmen, Iwai, Leo Kei, Rodrigues, Renata Santos, Yoneyama, Kelly Aparecida Geraldo, de Melo Rodrigues Ávila, Veridiana
• Format: Journal Article Web Resource
• Language: English
• Published: England Elsevier Ltd 01-07-2023
• Subjects: Animals; Chemistry; Chimie; Crotalid Venoms; Crotalid Venoms - chemistry; Crotalus; L-amino acid Oxidase; L-Amino Acid Oxidase - chemistry; Leishmania spp; Leishmanicidal activity; Physical, chemical, mathematical & earth Sciences; Physique, chimie, mathématiques & sciences de la terre; ROS; Snake venom; Snake Venoms; Toxicology; Snake venom; Leishmanicidal activity; L-amino acid Oxidase; ROS; Leishmania spp
• ISSN: 0041-0101; 1879-3150; 1879-3150
• DOI: 10.1016/j.toxicon.2023.107156

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.
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•CollinLAAO-I increased ROS production and caused mitochondrial damage in Leishmania.•CollinLAAO-I treatment interfered in essential steps of the Leishmania infection.•L. (L.) infantum is more susceptible to the leishmanicidal effect of CollinLAAO-I.