Abstract
High levels of methionine (Met) and its metabolites, such as methionine sulfoxide (MetO), found in hypermethioninemia, can be detrimental to the body; however, the underlying mechanisms are still uncertain. Using a recently standardized protocol, the aim of this study was to investigate the effects of chronic administration of Met and/or MetO on parameters of oxidative damage in the total brain, liver, and kidney of young mice. Swiss male mice were subcutaneously injected with Met and MetO at concentrations of 0.35–1.2 g/kg body weight and 0.09–0.3 g/kg body weight, respectively, from the 10th–38th day post-birth, while the control group was treated with saline solution. Results showed that Met and/or MetO caused an increase in reactive oxygen species (ROS) and lipoperoxidation, along with a reduction of superoxide dismutase (SOD) and catalase (CAT) activities in the brain. In the liver, Met and/or MetO enhanced ROS and nitrite levels, and reduced SOD, CAT, and delta aminolevulinic dehydratase activities. The effects on the kidney were an increase in ROS production and SOD activity, and a reduction in thiol content and CAT activity. These data demonstrated the contribution of redox imbalance to the systemic changes found in patients with hypermethioninemia. In conclusion, our findings may help future studies to better understand the pathophysiological mechanisms of hypermethioninemia as well as contribute to the search for new therapeutic agents for this pathology.
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Data availability
Datasets generated in the current study are available from the corresponding author on reasonable request.
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Acknowledgments
This research was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Rio Grande do Sul (FAPERGS). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior- Brasil (CAPES) – Finance code 001.
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Meine BM, Franceschi TS, Bona NP, Spohr L and Pedra NS performed experiments. Soares MSA, Spanevello RS, and Stefanello FM supervised experimental work and analysed data. Meine BM and Franceschi TS wrote the manuscript.
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The Ethics Committee of Animal Experimentation from the Federal University of Pelotas approved the experimental design and procedures used in this study (CEEA 9221–2013). Swiss male mice were requested and made available by the Central Animal House of the Federal University of Pelotas, Pelotas, RS, Brazil.
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de Moraes Meine, B., Franceschi, T.S., Bona, N.P. et al. Chemical hypermethioninemia in young mice: oxidative damage and reduction of antioxidant enzyme activity in brain, kidney, and liver. Metab Brain Dis 38, 223–232 (2023). https://doi.org/10.1007/s11011-022-01107-0
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DOI: https://doi.org/10.1007/s11011-022-01107-0