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Therapeutic Potential of Combined Therapy of Vitamin A and Vitamin C in the Experimental Autoimmune Encephalomyelitis (EAE) in Lewis Rats

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Abstract

Demyelination, inflammation, oxidative injury, and glial activation are the main pathological hallmarks of multiple sclerosis (MS). Vitamins, as essential micronutrients, seem to be crucial in the pathogenesis of MS, and particularly vitamins A and C were found to have a protective role in MS development or progression. In this study, the therapeutic potential of combined therapy of vitamins A and C on progression of experimental autoimmune encephalomyelitis (EAE) and myelin repair mechanisms was examined. EAE, an animal model of MS, was induced in female Lewis rats. The rats were treated with daily intraperitoneal injections of vitamins A and C and their combination. We found that co-supplementation of vitamins A and C mitigated neurological severity and EAE disease progression. Histological study confirmed a significant reduction in demyelination size, inflammation and immune cell infiltration as well as microglia and astrocyte activation following co-administration of vitamins A and C. Co-administration of vitamins A and C also decreased the levels of pro-inflammatory cytokines (TNF-α, IL1β) and iNOS and increased gene expressions of IL-10, Nrf-2, HO-1, and MBP. Combination therapy of vitamins A and C also increased the total antioxidant capacity and decreased levels of oxidative stress markers. Finally, we proved that co-administration of vitamins A and C has anti-apoptotic and neuroprotective impacts in EAE via decreasing caspase-3 and increasing BDNF and NeuN expressing cells. The present study suggests that combined therapy of vitamins A and C may be an effective strategy for development of alternative medicine in boosting myelin repair in demyelinating diseases.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to gratefully appreciate the kind support of Dr. Mohammad Javan from physiology department of Tarbiat Modares University Tehran-Iran during the study. Also we appreciate Babol University of Medical Sciences for the support and facilities used during the project.

Funding

This work was supported by a grant (No. 35425–139-02–96), from Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

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Authors and Affiliations

  1. Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Mojdeh Navidhamidi

  2. Department of Medical-Surgical Nursing and Basic Sciences, School of Nursing and Midwifery, Tehran University of Medical Sciences, Tehran, Iran

    Mojdeh Navidhamidi

  3. Neuroscience Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

    Atena Nazari

  4. Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran

    Samaneh Dehghan

  5. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

    Anahita Ebrahimpour, Reza Nasrnezhad & Fereshteh Pourabdolhossein

  6. Department of Physiology, School of Medicine, Babol University of Medical Sciences, Babol, Iran

    Fereshteh Pourabdolhossein

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  1. Mojdeh Navidhamidi
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Contributions

Mozhdeh Navidhamidi: conceptualization; investigation; data curation; funding acquisition; project administration; and writing—review & editing of the manuscript. Atena Nazari: methodology; investigation review & editing of the manuscript. Samaneh Deghan: investigation; formal analysis; review & editing of the manuscript. Anahita Ebrahimpour: investigation; review & editing of the manuscript. Reza Nasrnezhad: investigation; formal analysis Fereshteh Pourabdolhossein: Conceptualization; Investigation; Methodology; Data curation; funding acquisition; formal analysis; Software; Supervision; Validation; Writing—original draft; Writing—review & editing.

Corresponding author

Correspondence to Fereshteh Pourabdolhossein.

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Ethics approval and consent to participate

All experimental procedures of this study were performed according to the international guidelines for care and use of laboratory animals and approved (Ethic code number: IR.TUMS.VCR.REC.1396.3350) by the ethical committee of Tehran University of Medical Sciences. This article does not contain any studies involving human participants performed by any of the authors.

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Highlights

• Co-supplementation of vitamins A and C alleviated neurological symptoms of EAE disease

• Co-administration of vitamins A and C reduced gliosis, immune cell infiltration and demyelination in EAE

• Combination therapy of vitamins A and C increased the antioxidant capacity and decreased the oxidative stress

• Co-supplementation of vitamins A and C decreased TNF-α and IL-1β levels and increased IL-10

• Co-administration of vitamins A and C has anti-apoptotic and neuroprotective impacts in EAE model

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Navidhamidi, M., Nazari, A., Dehghan, S. et al. Therapeutic Potential of Combined Therapy of Vitamin A and Vitamin C in the Experimental Autoimmune Encephalomyelitis (EAE) in Lewis Rats. Mol Neurobiol 59, 2328–2347 (2022). https://doi.org/10.1007/s12035-022-02755-0

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