Pharmacological Investigation of CC-LAAO, an L-Amino Acid Oxidase from Snake Venom.
Fiche publication
Date publication
décembre 2021
Journal
Toxins
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MICHEAU Olivier
Tous les auteurs :
Abdelkafi-Koubaa Z, ELBini-Dhouib I, Souid S, Jebali J, Doghri R, Srairi-Abid N, Essafi-Benkhadir K, Micheau O, Marrakchi N
Lien Pubmed
Résumé
Snake venom proteins, which are responsible for deadly snakebite envenomation, induce severe injuries including neurotoxicity, myotoxicity, cardiotoxicity, hemorrhage, and the disruption of blood homeostasis. Yet, many snake-venom proteins have been developed as potential drugs for treating human diseases due to their pharmacological effects. In this study, we evaluated the use of, an L-amino acid oxidase isolated from snake venom CC-LAAO, as a potential anti-glioblastoma drug, by investigating its in vivo and in vitro pharmacological effects. Our results showed that acute exposure to CC-LAAO at 1 and 2.5 µg/mL does not induce significant toxicity on vital organs, as indicated by the murine blood parameters including aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) activities, and creatinine levels. The histopathological examination demonstrated that only at high concentrations did CC-LAAO induce inflammation and necrosis in several organs of the test subjects. Interestingly, when tested on human glioblastoma U87 cells, CC-LAAO induced a dose-dependent apoptotic effect through the HO generated during the enzymatic reaction. Taken altogether, our data indicated that low concentration of CC-LAAO may be safe and may have potential in the development of anti-glioblastoma agents.
Mots clés
SV-LAAOs, apoptosis, envenomation, glioblastoma cells, toxicity
Référence
Toxins (Basel). 2021 Dec 16;13(12):