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

Autor: Fonseca-Fonseca LA; Centro de Investigación y Desarrollo de Medicamentos, Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600, Ciudad de la Habana, Cuba., Nuñez-Figueredo Y; Centro de Investigación y Desarrollo de Medicamentos, Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600, Ciudad de la Habana, Cuba., Sánchez JR; Centro de Investigación y Desarrollo de Medicamentos, Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600, Ciudad de la Habana, Cuba., Guerra MW; Centro de Investigación y Desarrollo de Medicamentos, Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600, Ciudad de la Habana, Cuba., Ochoa-Rodríguez E; Laboratorio de Síntesis Orgánica. Departamento de Química Orgánica. Facultad de Química, Universidad de La Habana (Zapata s/n entre G y Carlitos Aguirre, Vedado, Plaza de la Revolución, CP 10400, Ciudad de la Habana, Cuba., Verdecia-Reyes Y; Laboratorio de Síntesis Orgánica. Departamento de Química Orgánica. Facultad de Química, Universidad de La Habana (Zapata s/n entre G y Carlitos Aguirre, Vedado, Plaza de la Revolución, CP 10400, Ciudad de la Habana, Cuba., Hernádez RD; Centro de Investigación y Desarrollo de Medicamentos, Ave 26, No. 1605 Boyeros y Puentes Grandes, CP 10600, Ciudad de la Habana, Cuba., Menezes-Filho NJ; Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia - UFBA, Av. Reitor Miguel Calmon s/n, Vale do Canela, Salvador, Bahia, CEP 41100-100, Brazil., Costa TCS; Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia - UFBA, Av. Reitor Miguel Calmon s/n, Vale do Canela, Salvador, Bahia, CEP 41100-100, Brazil., de Santana WA; Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia - UFBA, Av. Reitor Miguel Calmon s/n, Vale do Canela, Salvador, Bahia, CEP 41100-100, Brazil., Oliveira JL; Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia - UFBA, Av. Reitor Miguel Calmon s/n, Vale do Canela, Salvador, Bahia, CEP 41100-100, Brazil., Segura-Aguilar J; Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile., da Silva VDA; Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia - UFBA, Av. Reitor Miguel Calmon s/n, Vale do Canela, Salvador, Bahia, CEP 41100-100, Brazil., Costa SL; Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Universidade Federal da Bahia - UFBA, Av. Reitor Miguel Calmon s/n, Vale do Canela, Salvador, Bahia, CEP 41100-100, Brazil. costasl@ufba.br.
Jazyk: angličtina
Zdroj: Neurotoxicity research [Neurotox Res] 2019 Aug; Vol. 36 (2), pp. 279-291. Date of Electronic Publication: 2018 Jan 02.
DOI: 10.1007/s12640-017-9851-5
Abstrakt: 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 H 2 O 2 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.
Databáze: MEDLINE
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