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Dual Effect of Carnosine on ROS Formation in Rat Cultured Cortical Astrocytes

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Abstract

Carnosine is composed of β-alanine and L-histidine and is considered to be an important neuroprotective agent with antioxidant, metal chelating, and antisenescence properties. However, children with serum carnosinase deficiency present increased circulating carnosine and severe neurological symptoms. We here investigated the in vitro effects of carnosine on redox and mitochondrial parameters in cultured cortical astrocytes from neonatal rats. Carnosine did not alter mitochondrial content or mitochondrial membrane potential. On the other hand, carnosine increased mitochondrial superoxide anion formation, levels of thiobarbituric acid reactive substances and oxidation of 2′,7′-dichlorofluorescin diacetate (DCF-DA), indicating that carnosine per se acts as a pro-oxidant agent. Nonetheless, carnosine prevented DCF-DA oxidation induced by H2O2 in cultured cortical astrocytes. Since alterations on mitochondrial membrane potential are not likely to be involved in these effects of carnosine, the involvement of N-Methyl-D-aspartate (NMDA) receptors in the pro-oxidant actions of carnosine was investigated. MK-801, an antagonist of NMDA receptors, prevented DCF-DA oxidation induced by carnosine in cultured cortical astrocytes. Astrocyte reactivity induced by carnosine was also prevented by the coincubation with MK-801. The present study shows for the very first time the pro-oxidant effects of carnosine per se in astrocytes. The data raise awareness on the importance of a better understanding of the biological actions of carnosine, a nutraceutical otherwise widely reported as devoid of side effects.

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Acknowledgements

We thank Victor Túlio Resende for contributing with training in microscopy and suggestions in that area.

Funding

This study was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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Authors and Affiliations

  1. Laboratório de Erros Inatos do Metabolismo, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Fabiola Diniz, Belisa Parmeggiani, Gabriela Brandão, Bruna Klippel Ferreira, Monique Fonseca Teixeira, Patricia Fernanda Schuck & Gustavo Costa Ferreira

  2. Programa de Pós-Graduação em Ciências Biológicas:Biofísica, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Fabiola Diniz, Ricardo Augusto de Melo Reis & Gustavo Costa Ferreira

  3. Section of Pediatric Nephrology, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA, United States

    Fabiola Diniz

  4. Laboratório de Doenças Neurometabólicas, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Brazil

    Emilio Luiz Streck

  5. Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay

    Silvia Olivera-Bravo

  6. Institut Pasteur de Montevideo, Montevideo, Uruguay

    Luis Hector Barbeito

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  1. Fabiola Diniz
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Contributions

F.C.D: conception and design, collection and assembly of the data, data analysis and interpretation, manuscript writing, and final approval of the manuscript. B.P.; G.B., B.K.F., and M.F.T.: collection and assembly of the data, data analysis and interpretation, and final approval of the manuscript. E.L.S.; S.O.B.; L.H.B.; P.F.S. and R.A.M.R.: conception and design, assembly of the data, data interpretation, final approval of manuscript. G.C.F.: conception and design, assembly of the data, data analysis and interpretation, manuscript writing, final approval of manuscript, financial support, and administrative support.

Corresponding author

Correspondence to Gustavo Costa Ferreira.

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Institutional Review Board Statement

This study was approved by the Animal Research Ethics Committee of the Universidade Federal do Rio de Janeiro (protocol # 091-20). This study was performed in accordance with the “Guide for the Care and Use of Laboratory Animals: Eighth Edition” (The National Academies Collection: Reports funded by National Institutes of Health, 2011) and the Brazilian Directive for the Care and Use of Animals for Scientific and Didactic Purposes (2018).

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Diniz, F., Parmeggiani, B., Brandão, G. et al. Dual Effect of Carnosine on ROS Formation in Rat Cultured Cortical Astrocytes. Mol Neurobiol (2023). https://doi.org/10.1007/s12035-023-03880-0

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