Protective Effects of Zonisamide Against Rotenone-Induced Neurotoxicity

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• 作者：Salvatore Condello (1)
  Monica Curr(1)
  Nadia Ferlazzo (1)
  Gregorio Costa (2)
  Giuseppa Visalli (1)
  Daniela Caccamo (1)
  Laura Rosa Pisani (3)
  Cinzia Costa (4) (5)
  Paolo Calabresi (4) (5)
  Riccardo Ientile (1)
  Francesco Pisani (3)
  
• 关键词：Zonisamide ; Neuroprotection ; Oxidative stress ; Mitochondrial impairment ; Apoptosis
• 刊名：Neurochemical Research
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：38
• 期：12
• 页码：2631-2639
• 全文大小：
• 作者单位：Salvatore Condello (1)
  Monica Curr(1)
  Nadia Ferlazzo (1)
  Gregorio Costa (2)
  Giuseppa Visalli (1)
  Daniela Caccamo (1)
  Laura Rosa Pisani (3)
  Cinzia Costa (4) (5)
  Paolo Calabresi (4) (5)
  Riccardo Ientile (1)
  Francesco Pisani (3)
  
  1. Department of Biomedical Sciences and Morphological and Functional Imaging, University of Messina, AOU Policlinico . Martino Via C. Valeria, 98125, Messina, Italy
  2. Department of Human Pathology, Laboratory of Immunology and Biotherapy, University of Messina, AOU . Martino Via C. Valeria, 98125, Messina, Italy
  3. Department of Neurosciences, Neurology Clinic, University of Messina, AOU . Martino Via C. Valeria, 98125, Messina, Italy
  4. Neurology Clinic, Ospedale Santa Maria Della Misericordia, University of Perugia, Via Santa Andrea Delle Fratte, San Sisto, 06158, Perugia, Italy
  5. IRCCS Fondazione S. Lucia, Via Ardeatina 306, 00179, Rome, Italy
  
• ISSN：1573-6903

文摘

Zonisamide (ZNS), an antiepileptic drug having beneficial effects also against Parkinson 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 24h to 500 nM rotenone with or without pre-treatment with 1000 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) displayed significant protective effects against rotenone-induced ROS production and at 4 and 12h respectively, reaching the maximal extent at 24h. 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.