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Effects of lipoic acid supplementation on age- and iron-induced memory impairment, mitochondrial DNA damage and antioxidant responses

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Abstract

Purpose

To investigate the effects of lipoic acid (LA) supplementation during adulthood combined with supplementation later in life or LA administration only at old age on age-induced cognitive dysfunction, mitochondrial DNA deletions, caspase 3 and antioxidant response enzymes expression in iron-treated rats.

Methods

Male rats were submitted to iron treatment (30 mg/kg body wt of Carbonyl iron) from 12 to 14th post-natal days. Iron-treated rats received LA supplementation (50 mg/kg, daily) in adulthood and old age or at old age only for 21 days. Memory, mitochondrial DNA (mtDNA) complex I deletions, caspase 3 mRNA expression and antioxidant response enzymes mRNA expression were analyzed in the hippocampus.

Results

LA administration in adulthood combined with treatment later in life was able to reverse age-induced effects on object recognition and inhibitory avoidance memory, as well as on mtDNA deletions, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression, and antioxidant enzymes disruption induced by iron in aged rats. LA treatment only at old age reversed iron-induced effects to a lesser extent when compared to the combined treatment.

Conclusion

The present findings support the view that LA supplementation may be considered as an adjuvant against mitochondrial damage and cognitive decline related to aging and neurodegenerative disorders.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Funding

This work was supported by National Council for Scientific and Technological Development [CNPq; grant numbers 305656/2019-8 and 421643/2016-1 to N.S.]; the National Institute of Science and Technology for Translational Medicine [INCT-TM – grant number 465458/2014-9]; National Institute of Science and Technology for Brain Diseases, Excitotoxicity and Neuroprotection [INCT-EN—Grant number 465671/2014-4]; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001. M.R.B and N.S are Research Career Awardees of the CNPq. The funding sources had no involvement in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

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Authors and Affiliations

  1. Laboratory of Genomics and Molecular Biology, School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil

    Patrícia Molz, Kesiane Mayra da Costa, Luiza Wilges Kist & Maurício Reis Bogo

  2. Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil

    Patrícia Molz, Betânia Souza de Freitas & Vanise Hallas Uberti

  3. Graduate Program in Medicine and Health Sciences, School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil

    Patrícia Molz, Kesiane Mayra da Costa & Maurício Reis Bogo

  4. National Institute of Science and Technology for Brain Diseases, Excitotoxicity and Neuroprotection (INCT-EN), Porto Alegre, Brazil

    Maurício Reis Bogo

  5. National Institute of Science and Technology for Translational Medicine (INCT-TM), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brasília, Brazil

    Nadja Schröder

  6. Department of Physiology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500, Porto Alegre, Brazil

    Nadja Schröder

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  1. Patrícia Molz
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  2. Betânia Souza de Freitas
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  3. Vanise Hallas Uberti
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Contributions

PM: conceptualization, methodology, investigation, writing—original draft. BSdF: investigation, resources, project administration. VHU: investigation. KMdC: investigation. LWK: investigation, validation. MRB: conceptualization, methodology, validation, writing—review and editing, funding acquisition. NS: conceptualization, methodology, validation, formal analysis, writing—original draft, writing—review and editing, supervision, project administration, funding acquisition.

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Correspondence to Nadja Schröder.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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This study was approved by the Institutional Ethics Committee for the Use of Animals of the Pontifical Catholic University (CEUA SIPESQ #7510) and all experimental procedures were performed in accordance with the Brazilian Guidelines for the Care and Use of Animals in Research and Teaching (DBCA, published by CONCEA, MCTI, Brazil).

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Molz, P., de Freitas, B.S., Uberti, V.H. et al. Effects of lipoic acid supplementation on age- and iron-induced memory impairment, mitochondrial DNA damage and antioxidant responses. Eur J Nutr 60, 3679–3690 (2021). https://doi.org/10.1007/s00394-021-02541-z

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