Abstract
Maple syrup urine disease (MSUD) is an inherited metabolic disorder caused by a deficiency in branched-chain alpha-ketoacid dehydrogenase complex (BCKAC). The treatment is a standard therapy based on a protein-restricted diet with low branched-chain amino acids (BCAA) content to reduce plasma levels and, consequently, the effects of accumulating their metabolites, mainly in the central nervous system. Although the benefits of dietary therapy for MSUD are undeniable, natural protein restriction may increase the risk of nutritional deficiencies, resulting in a low total antioxidant status that can predispose and contribute to oxidative stress. As MSUD is related to redox and energy imbalance, melatonin can be an important adjuvant treatment. Melatonin directly scavenges the hydroxy radical, peroxyl radical, nitrite anion, and singlet oxygen and indirectly induces antioxidant enzyme production. Therefore, this study assesses the role of melatonin treatment on oxidative stress in brain tissue and behavior parameters of zebrafish (Danio rerio) exposed to two concentrations of leucine-induced MSUD: leucine 2 mM and 5mM; and treated with 100 nM of melatonin. Oxidative stress was assessed through oxidative damage (TBARS, DCF, and sulfhydryl content) and antioxidant enzyme activity (SOD and CAT). Melatonin treatment improved redox imbalance with reduced TBARS levels, increased SOD activity, and normalized CAT activity to baseline. Behavior was analyzed with novel object recognition test. Animals exposed to leucine improved object recognition due to melatonin treatment. With the above, we can suggest that melatonin supplementation can protect neurologic oxidative stress, protecting leucine-induced behavior alterations such as memory impairment.
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All data generated or analyzed during this study are included in this published article and available upon request.
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This research was supported by the Higher Education Personnel (CAPES), the Brazilian National Council for Scientific and Technological Development (CNPq), the Santa Catarina State Research and Innovation Support Foundation (Fapesc), and the University of Southern Santa Catarina (UNESC).
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This research was supported by the Higher Education Personnel (CAPES), the Brazilian National Council for Scientific and Technological Development (CNPq), the Santa Catarina State Research and Innovation Support Foundation (Fapesc), and the University of Southern Santa Catarina (UNESC).
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Conception and design of the research: Mariane Bernardo Duarte, Bianca Zampiroli de Medeiros, Eduardo Pacheco Rico, Emílio Luiz Streck. Acquisition of data: Mariane Bernardo Duarte, Isabela da Silva Lemos, Guilherme Lodetti da Silva, Eduardo Ronconi Dondossola, Carolina Antunes Torres. Analysis and interpretation of the data: Isabela da Silva Lemos. Obtaining financing: Emílio Luiz Streck. Writing of the manuscript: Mariane Bernardo Duarte, Pauline Souza Effting, Isabela da Silva Lemos. Critical revision of the manuscript for intellectual content: Pauline Souza Effting, Emílio Luiz Streck.
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Duarte, M.B., Medeiros, B.Z., da Silva Lemos, I. et al. Melatonin improves behavioral parameters and oxidative stress in zebrafish submitted to a leucine-induced MSUD protocol. Metab Brain Dis 38, 2105–2114 (2023). https://doi.org/10.1007/s11011-023-01220-8
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DOI: https://doi.org/10.1007/s11011-023-01220-8