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Exposure to leucine induces oxidative stress in the brain of zebrafish

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Abstract

Maple Syrup Urine Disease (MSUD) is an autosomal recessive inherited disorder caused by a deficiency in the activity of the branched-chain alpha-ketoacid dehydrogenase complex leading to the accumulation of branched-chain amino acids (BCAA) leucine, isoleucine, and valine and their respective branched-chain α-ketoacids and corresponding hydroxy acids. Considering that Danio rerio, known as zebrafish, has been widely used as an experimental model in several research areas because it has favorable characteristics that complement other experimental models, this study aimed to evaluate oxidative stress parameters in zebrafish exposed to high levels of leucine (2 mM and 5 mM), in a model similar of MSUD. Twenty-four hours after exposure, the animals were euthanized, and the brain content dissected for analysis of oxidative stress parameters: thiobarbituric acid reactive substances (TBARS), 2′,7′-dichlorofluorescein oxidation assay (DCF); content of sulfhydryl, and superoxide dismutase (SOD) and catalase (CAT) activities. Animals exposed to 2 mM and 5 mM leucine showed an increase in the measurement of TBARS and decreased sulfhydryl content. There were no significant changes in DCF oxidation. In addition, animals exposed to 2 mM and 5 mM leucine were found to have decreased SOD activity and increased CAT activity. Based on these results, exposure of zebrafish to high doses of leucine can act as a promising animal model for MSUD, providing a better understanding of the toxicity profile of leucine exposure and its use in future investigations and strategies related to the pathophysiology of MSUD.

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Data availability

The data that support the findings of this study are available on request from the corresponding author.

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Funding

This research was supported by grants from Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina (FAPESC) and Universidade do Extremo Sul Catarinense (UNESC).

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Authors and Affiliations

  1. Laboratório de Doenças Neurometabólicas, Laboratório de Neurologia Experimental, Programa de Pós-Graduação Em Ciências da Saúde, Universidade Do Extremo Sul Catarinense, Criciúma, SC, Brasil

    Bianca Z. de Medeiros, Leticia B. Wessler, Mariane B. Duarte, Isabela S. Lemos, Gabriela Candiotto, Rafael O. Canarim, Paulo C. L. dos Santos, Carolina A. Torres, Eduardo P. Rico & Emilio L. Streck

  2. Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    Giselli Scaini

  3. Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação Em Ciências da Saúde, Universidade Do Extremo Sul Catarinense, Criciúma, SC, Brasil

    Jaqueline S. Generoso

Authors
  1. Bianca Z. de Medeiros
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  2. Leticia B. Wessler
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  9. Giselli Scaini
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  12. Emilio L. Streck
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Contributions

BZM, GS, EPR, JSG and ELS designed the study; LBW, MBD, ISL, GC, ROC, PCLS and CAT conducted the experiments and analyzed the data; BZM, GS, JSG and ELS prepared the manuscript; GS and ELS performed the analysis of the manuscript. All authors contributed to this research work and the development of the final manuscript.

Corresponding author

Correspondence to Emilio L. Streck.

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All the experimental procedures were carried according to the National Institutes of Health Guide for Care and Use of Laboratory Animal and approved by the Animal Care and Experimentation Committee of UNESC (protocol number 062/2018-1).

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All authors have reviewed the contents of the manuscript, have an approved of its contents and validated the accuracy of the data and they have no financial or personal conflicts of interest related to this work.

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de Medeiros, B.Z., Wessler, L.B., Duarte, M.B. et al. Exposure to leucine induces oxidative stress in the brain of zebrafish. Metab Brain Dis 37, 1155–1161 (2022). https://doi.org/10.1007/s11011-022-00934-5

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