title: Protective effects of zonisamide against rotenone-induced neurotoxicity.
abstract: Zonisamide (ZNS), an antiepileptic drug having beneficial effects also against Parkinson's disease symptoms, has proven to display an antioxidant effects in different experimental models. In the present study, the effects of ZNS on rotenone-induced cell injury were investigated in human neuroblastoma SH-SY5Y cells differentiated towards a neuronal phenotype. Cell cultures were exposed for 24 h to 500 nM rotenone with or without pre-treatment with 10-100 μM ZNS. Then, the following parameters were analyzed: (a) cell viability; (b) intracellular reactive oxygen species production; (c) mitochondrial transmembrane potential; (d) cell necrosis and apoptosis; (e) caspase-3 activity. ZNS dose-dependently suppressed rotenone-induced cell damage through a decrease in intracellular ROS production, and restoring mitochondrial membrane potential. Similarly to ZNS effects, the treatment with N-acetyl-cysteine (100 μM) displayed significant protective effects against rotenone-induced ROS production and Δψm at 4 and 12 h respectively, reaching the maximal extent at 24 h. Additionally, ZNS displayed antiapoptotic effects, as demonstrated by flow cytometric analysis of annexin V/propidium iodide double staining, and significant attenuated rotenone-increased caspase 3 activity. On the whole, these findings suggest that ZNS preserves mitochondrial functions and counteracts apoptotic signalling mechanisms mainly by an antioxidant action. Thus, ZNS might have beneficial effect against neuronal cell degeneration in different experimental models involving mitochondrial dysfunction.
authors.affiliation: Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, AOU Policlinico "G. Martino", Via C. Valeria, 98125, Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Condello
authors.forename: Monica
authors.initials: M
authors.lastname: Currò
authors.forename: Nadia
authors.initials: N
authors.lastname: Ferlazzo
authors.forename: Gregorio
authors.initials: G
authors.lastname: Costa
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Visalli
authors.forename: Daniela
authors.initials: D
authors.lastname: Caccamo
authors.forename: Laura Rosa
authors.initials: LR
authors.lastname: Pisani
authors.forename: Cinzia
authors.initials: C
authors.lastname: Costa
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ientile
authors.forename: Francesco
authors.initials: F
authors.lastname: Pisani
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity*; D000078305:Zonisamide
chemical_list: D007555:Isoxazoles; D017382:Reactive Oxygen Species; D012402:Rotenone; D000078305:Zonisamide