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01-08-2019 | ORIGINAL ARTICLE

KM-34, a Novel Antioxidant Compound, Protects against 6-Hydroxydopamine-Induced Mitochondrial Damage and Neurotoxicity

Authors: Luis Arturo Fonseca-Fonseca, Yanier Nuñez-Figueredo, Jeney Ramírez Sánchez, Maylin Wong Guerra, Estael Ochoa-Rodríguez, Yamila Verdecia-Reyes, René Delgado Hernádez, Noelio J. Menezes-Filho, Teresa Cristina Silva Costa, Wagno Alcântara de Santana, Joana L. Oliveira, Juan Segura-Aguilar, Victor Diogenes Amaral da Silva, Silva Lima Costa

Published in: Neurotoxicity Research | Issue 2/2019

Abstract

The etiology of Parkinson’s disease is not completely understood and is believed to be multifactorial. Neuronal disorders associated to oxidative stress and mitochondrial dysfunction are widely considered major consequences. The aim of this study was to investigate the effect of the synthetic arylidenmalonate derivative 5-(3,4-dihydroxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (KM-34), in oxidative stress and mitochondrial dysfunction induced by 6-hydroxydopamine (6-OHDA). Pretreatment (2 h) with KM-34 (1 and 10 μM) markedly attenuated 6-OHDA-induced PC12 cell death in a concentration-dependent manner. KM-34 also inhibited H₂O₂ generation, mitochondrial swelling, and membrane potential dissipation after 6-OHDA-induced mitochondrial damage. In vivo, KM-34 treatment (1 and 2 mg/Kg) reduced percentage of asymmetry (cylinder test) and increased the vertical exploration (open field) with respect to untreated injured animals; KM-34 also reduced glial fibrillary acidic protein overexpression and increased tyrosine hydroxylase-positive cell number, both in substantia nigra pars compacta. These results demonstrate that KM-34 present biological effects associated to mitoprotection and neuroprotection in vitro, moreover, glial response and neuroprotection in SNpc in vivo. We suggest that KM-34 could be a putative neuroprotective agent for inhibiting the progressive neurodegenerative disease associated to oxidative stress and mitochondrial dysfunction.

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Title: KM-34, a Novel Antioxidant Compound, Protects against 6-Hydroxydopamine-Induced Mitochondrial Damage and Neurotoxicity
Authors: Luis Arturo Fonseca-Fonseca
Yanier Nuñez-Figueredo
Jeney Ramírez Sánchez
Maylin Wong Guerra
Estael Ochoa-Rodríguez
Yamila Verdecia-Reyes
René Delgado Hernádez
Noelio J. Menezes-Filho
Teresa Cristina Silva Costa
Wagno Alcântara de Santana
Joana L. Oliveira
Juan Segura-Aguilar
Victor Diogenes Amaral da Silva
Silva Lima Costa
Publication date: 01-08-2019
Publisher: Springer US
Published in: Neurotoxicity Research / Issue 2/2019
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-017-9851-5

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KM-34, a Novel Antioxidant Compound, Protects against 6-Hydroxydopamine-Induced Mitochondrial Damage and Neurotoxicity

Abstract

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Abstract

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