JM-20, a novel hybrid molecule, protects against rotenone-induced neurotoxicity in experimental model of Parkinson's disease
| Autor: | Silvia Lima Costa, Yanier Nuñez-Figueredo, Maylin Wong-Guerra, Padrón Yaquis Alejandro Saúl, Jeney Ramírez-Sánchez, Yanay Montano-Peguero, Victor Diogenes Amaral da Silva, Luis Arturo Fonseca-Fonseca, Gilberto L. Pardo-Andreu, Mondelo Rodriguez Abel |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Mitochondrion Pharmacology Motor Activity medicine.disease_cause Neuroprotection Niacin Superoxide dismutase 03 medical and health sciences chemistry.chemical_compound Benzodiazepines 0302 clinical medicine In vivo Rotenone medicine Animals Humans Cells Cultured biology Cell Death Superoxide Dismutase General Neuroscience Body Weight Neurotoxicity Brain Malondialdehyde medicine.disease Catalase Mitochondria Rats Oxidative Stress 030104 developmental biology Neuroprotective Agents chemistry biology.protein Neurotoxicity Syndromes 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Neuroscience letters. 690 |
| ISSN: | 1872-7972 |
| Popis: | Oxidative stress and mitochondrial dysfunction are two pathophysiological factors often associated with the neurodegenerative process involved in Parkinson's disease (PD). The aim of this study was to investigate the effects of a novel hybrid molecule, named JM-20, in different in vitro and in vivo models of PD induced by rotenone. To perform in vitro studies, SHSY-5Y cells were exposed to rotenone and/or treated with JM-20. To perform in vivo studies male Wistar rats were intoxicated with rotenone (2.5 mg/kg) via intraperitoneal injection and/or treated with JM-20 (40 mg/kg) administered via oral (for 25 days, both treatment). Rats were evaluated for global motor activity by measurement of locomotor activity. In addition, the effects on mortality, general behavior and redox parameters were also investigated. JM-20 protected SHSY-5Y cells against rotenone-induced cytotoxicity, evidenced by a significant diminution of cell death. In in vivo studies, JM-20 prevented rotenone-induced vertical exploration and locomotion frequency reductions, moreover prevented body weight loss and mortality induced by rotenone. It also improved the redox state of rotenone-exposured animals by increasing superoxide dismutase and catalase activities, total tissue-SH levels and decreasing malondialdehyde concentrations. Finally, JM-20 inhibited spontaneous mitochondrial swelling and membrane potential dissipation in isolated rats brain mitochondria. These results demonstrate that JM-20 is a potential neuroprotective agent against rotenone-induced damage in both in vitro and in vivo models, resulting in reduced neuronal oxidative injury and protection of mitochondria from impairment. |
| Databáze: | OpenAIRE |
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