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Preliminary results of PBA-loaded nanoparticles development and the effect on oxidative stress and neuroinflammation in rats submitted to a chemically induced chronic model of MSUD.
Mescka, Caroline Paula; de Moura Coelho, Daniella; Sitta, Angela; Catarino, Felipe; Donida, Bruna; Rosa, Andrea Pereira; Gonzalez, Esteban Alberto; Pinheiro, Camila Vieira; Poletto, Fernanda; Baldo, Guilherme; Dutra-Filho, Carlos Severo; Vargas, Carmen Regla.
Afiliación
  • Mescka CP; Programa de Pós-Graduação em Ciências Farmacêuticas, UFRGS, Av. Ipiranga, 2752, Porto Alegre, RS, 90610-000, Brazil. carolmescka@yahoo.com.br.
  • de Moura Coelho D; Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-903, Brazil.
  • Sitta A; Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-903, Brazil.
  • Catarino F; Serviço de Genética Médica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-903, Brazil.
  • Donida B; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-000, Brazil.
  • Rosa AP; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, UFRGS, Rua Ramiro Barcelos, 2600, Porto Alegre, RS, 90035-000, Brazil.
  • Gonzalez EA; Centro de Terapia Gênica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-903, Brazil.
  • Pinheiro CV; Programa de Pós-Graduação em Genética e Biologia Molecular, UFRGS, Avenida Bento Gonçalves, 9500, Porto Alegre, RS, 91501-970, Brazil.
  • Poletto F; Centro de Terapia Gênica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-903, Brazil.
  • Baldo G; Departamento de Química Orgânica, Instituto de Química, UFRGS, Avenida Bento Gonçalves, 9500, Porto Alegre, RS, 91501-970, Brazil.
  • Dutra-Filho CS; Centro de Terapia Gênica, HCPA, UFRGS, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-903, Brazil.
  • Vargas CR; Programa de Pós-Graduação em Ciências Biológicas: Fisiologia, UFRGS, Rua Sarmento Leite, 500, Porto Alegre, RS, 90050-170, Brazil.
Metab Brain Dis ; 36(5): 1015-1027, 2021 06.
Article en En | MEDLINE | ID: mdl-33620579
Maple syrup urine disease (MSUD) is a genetic disorder that leads the accumulation of branched-chain amino acids (BCAA) leucine (Leu), isoleucine, valine and metabolites. The symptomatology includes psychomotor delay and mental retardation. MSUD therapy comprises a lifelong protein strict diet with low BCAA levels and is well established that high concentrations of Leu and/or its ketoacid are associated with neurological symptoms. Recently, it was demonstrated that the phenylbutyrate (PBA) have the ability to decrease BCAA concentrations. This work aimed the development of lipid-based nanoparticles loaded with PBA, capable of targeting to the central nervous system in order to verify its action mechanisms on oxidative stress and cell death in brain of rats subjected to a MSUD chronic model. PBA-loaded nanoparticles treatment was effective in significantly decreasing BCAA concentration in plasma and Leu in the cerebral cortex of MSUD animals. Furthermore, PBA modulate the activity of catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase enzymes, as well as preventing the oxidative damage to lipid membranes and proteins. PBA was also able to decrease the glial fibrillary acidic protein concentrations and partially decreased the reactive species production and caspase-3 activity in MSUD rats. Taken together, the data indicate that the PBA-loaded nanoparticles could be an efficient adjuvant in the MSUD therapy, protecting against oxidative brain damage and neuroinflammation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenilbutiratos / Corteza Cerebral / Estrés Oxidativo / Nanopartículas / Aminoácidos de Cadena Ramificada / Enfermedad de la Orina de Jarabe de Arce Límite: Animals Idioma: En Revista: Metab Brain Dis Asunto de la revista: CEREBRO / METABOLISMO Año: 2021 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fenilbutiratos / Corteza Cerebral / Estrés Oxidativo / Nanopartículas / Aminoácidos de Cadena Ramificada / Enfermedad de la Orina de Jarabe de Arce Límite: Animals Idioma: En Revista: Metab Brain Dis Asunto de la revista: CEREBRO / METABOLISMO Año: 2021 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos