title: Evaluation of the neurotoxic/neuroprotective role of organoselenides using differentiated human neuroblastoma SH-SY5Y cell line challenged with 6-hydroxydopamine.
abstract: It is well established that oxidative stress plays a major role in several neurodegenerative conditions, like Parkinson disease (PD). Hence, there is an enormous effort for the development of new antioxidants compounds with therapeutic potential for the management of PD, such as synthetic organoselenides molecules. In this study, we selected between nine different synthetic organoselenides the most eligible ones for further neuroprotection assays, using the differentiated human neuroblastoma SH-SY5Y cell line as in vitro model. Neuronal differentiation of exponentially growing human neuroblastoma SH-SY5Y cells was triggered by cultivating cells with DMEM/F12 medium with 1% of fetal bovine serum (FBS) with the combination of 10 μM retinoic acid for 7 days. Differentiated cells were further incubated with different concentrations of nine organoselenides (0.1, 0.3, 3, 10, and 30 μM) for 24 h and cell viability, neurites densities and the immunocontent of neuronal markers were evaluated. Peroxyl radical scavenging potential of each compound was determined with TRAP assay. Three organoselenides tested presented low cytotoxicity and high antioxidant properties. Pre-treatment of cells with those compounds for 24 h lead to a significantly neuroprotection against 6-hydroxydopamine (6-OHDA) toxicity, which were directly related to their antioxidant properties. Neuroprotective activity of all three organoselenides was compared to diphenyl diselenide (PhSe)₂, the simplest of the diaryl diselenides tested. Our results demonstrate that differentiated human SH-SY5Y cells are suitable cellular model to evaluate neuroprotective/neurotoxic role of compounds, and support further evaluation of selected organoselenium molecules as potential pharmacological and therapeutic drugs in the treatment of PD.
authors.affiliation: Departamento de Bioquímica, Laboratório 24, ICBS/Universidade Federal do Rio Grande do Sul-UFRGS, Porto Alegre, RS 90035-003, Brazil.
authors.forename: Fernanda Martins
authors.initials: FM
authors.lastname: Lopes
authors.forename: Giovana Ferreira
authors.initials: GF
authors.lastname: Londero
authors.forename: Liana Marengo
authors.initials: LM
authors.lastname: de Medeiros
authors.forename: Leonardo Lisbôa
authors.initials: LL
authors.lastname: da Motta
authors.forename: Guilherme Antônio
authors.initials: GA
authors.lastname: Behr
authors.forename: Valeska Aguiar
authors.initials: VA
authors.lastname: de Oliveira
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ibrahim
authors.forename: José Cláudio Fonseca
authors.initials: JC
authors.lastname: Moreira
authors.forename: Lisiane de Oliveira
authors.initials: LO
authors.lastname: Porciúncula
authors.forename: João Batista Teixeira
authors.initials: JB
authors.lastname: da Rocha
authors.forename: Fábio
authors.initials: F
authors.lastname: Klamt
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D000978:Antiparkinson Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival; D004396:Coloring Agents; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D016566:Organoselenium Compounds / Q000494:pharmacology* / Q000633:toxicity*; D016627:Oxidopamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D013565:Sympatholytics / Q000037:antagonists & inhibitors / Q000633:toxicity*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D000975:Antioxidants; D000978:Antiparkinson Agents; D004396:Coloring Agents; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; D013565:Sympatholytics; D013778:Tetrazolium Salts; D013844:Thiazoles; D016627:Oxidopamine; C022616:thiazolyl blue; D005978:Glutathione