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
| Autor: | Caroline Paula Mescka, Fernanda Poletto, Bruna Donida, Andrea Pereira Rosa, Camila Vieira Pinheiro, Esteban Alberto Gonzalez, Felipe Maciel Catarino, Carlos Severo Dutra-Filho, Guilherme Baldo, Angela Sitta, Daniella de Moura Coelho, Carmen Regla Vargas |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Antioxidant medicine.medical_treatment Glutathione reductase Pharmacology medicine.disease_cause Biochemistry Phenylbutyrate Neuroprotection Superoxide dismutase 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Maple Syrup Urine Disease parasitic diseases medicine Animals Rats Wistar Cerebral Cortex chemistry.chemical_classification Glutathione Peroxidase biology Superoxide Dismutase Maple syrup urine disease Glutathione peroxidase nutritional and metabolic diseases Catalase medicine.disease Phenylbutyrates Rats Oxidative Stress 030104 developmental biology chemistry biology.protein Nanoparticles Neurology (clinical) Amino Acids Branched-Chain 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Metabolic Brain Disease. 36:1015-1027 |
| ISSN: | 1573-7365 0885-7490 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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