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Effects of resveratrol on alterations in cerebrum energy metabolism caused by metabolites accumulated in type I citrullinemia in rats

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Abstract

We investigated the in vitro effects of citrulline (0.1, 2.5 and 5.0 mM) and ammonia (0.01, 0.1 and 1.0 mM), and the influence of resveratrol (0.01 mM, 0.1 mM and 0.5 mM) on pyruvate kinase, citrate synthase, succinate dehydrogenase (SDH), complex II, and cytochrome c oxidase activities in cerebral cortex, cerebellum and hippocampus homogenates of 60-day-old male Wistar rats. Results showed that 2.5 and 5.0 mM citrulline decreased pyruvate kinase activity in cerebral cortex and, at a concentration of 5.0 mM, increased its activity in hippocampus. Additionally, 5.0 mM citrulline increased citrate synthase activity in the cerebellum of rats. Citrulline (5.0 mM) reduced complex II and cytochrome c oxidase activities in cerebral cortex and hippocampus. With regard to ammonia, at 0.1 and 1.0 mM, decreased complex II activity in cerebral cortex and at 1.0 mM decreased its activity in cerebellum and hippocampus. Ammonia (1.0 mM) also decreased cytochrome c oxidase activity in cerebral cortex and cerebellum of rats. Resveratrol was able to prevent most of the alterations caused by these metabolites in the biomarkers of energy metabolism measured in the cerebrum of rats. Data suggest that these alterations in energy metabolism, caused by citrulline and ammonia, are probably mediated by the generation of free radicals, which can in turn be scavenged by resveratrol.

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Funding

This work was supported by grants from Universidade da Região de Joinville (UNIVILLE).

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Authors and Affiliations

  1. Programa de Pós Graduação em Saúde e Meio Ambiente, Universidade da Região de Joinville – UNIVILLE, Rua Paulo Malschitzki,10- Zona Industrial Norte, Joinville, SC, 89201-972, Brazil

    Karine Louize Vincenzi, Larissa Delmônego, Aline Barbosa Lima & Daniela Delwing-de Lima

  2. Departamento de Medicina, Universidade da Região de Joinville – UNIVILLE, Rua Paulo Malschitzki, 10- Zona Industrial Norte, Joinville, SC, 89201-972, Brazil

    Thayna Patachini Maia & Daniela Delwing-de Lima

  3. Departamento de Farmácia, Universidade da Região de Joinville – UNIVILLE, Rua Paulo Malschitzki, 10- Zona Industrial Norte, Joinville, SC, 89201-972, Brazil

    Luana Carla Pscheidt

  4. Departamento de Ciências Naturais, Centro de Ciências Exatas e Naturais, Universidade Regional de Blumenau, Rua Antônio daVeiga,140, Blumenau, SC, 89012-900, Brazil

    Débora Delwing-Dal Magro

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  1. Karine Louize Vincenzi
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  2. Thayna Patachini Maia
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  3. Larissa Delmônego
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Contributions

All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All data were generated in-house, and no paper mill was used. K.L.V.: investigation, writing—original draft, writing—review and editing, visualization; T.P.M.: investigation, writing—original draft, writing—review and editing, visualization; L. D.: investigation; A.B.L.: investigation; L.C.P.: investigation; D.D.-D.M.: conceptualization, methodology, formal analysis, writing—review and editing, visualization; D.D.-deL.: conceptualization, methodology, formal analysis, writing—original draft, writing—review and editing, visualization, supervision. We are grateful for the collaboration of the research fellow (PIPE/Article 170) Ramon Fernandes Olm (Regional University of Blumenau).

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Correspondence to Daniela Delwing-de Lima.

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Vincenzi, K.L., Maia, T.P., Delmônego, L. et al. Effects of resveratrol on alterations in cerebrum energy metabolism caused by metabolites accumulated in type I citrullinemia in rats. Naunyn-Schmiedeberg's Arch Pharmacol 394, 873–884 (2021). https://doi.org/10.1007/s00210-020-02017-7

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