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Therapeutic Potential of Combined Therapy of Vitamin a and Vitamin C in the Experimental Autoimmune Encephalomyelitis (Eae) in Lewis Rats Publisher Pubmed



Navidhamidi M1, 2 ; Nazari A3 ; Dehghan S4 ; Ebrahimpour A5 ; Nasrnezhad R5 ; Pourabdolhossein F5, 6
Authors
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Authors Affiliations
  1. 1. Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Medical-Surgical Nursing and Basic Sciences, School of Nursing and Midwifery, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Neuroscience Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  4. 4. Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran
  5. 5. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
  6. 6. Department of Physiology, School of Medicine, Babol University of Medical Sciences, Babol, Iran

Source: Molecular Neurobiology Published:2022


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. Graphical abstract: [Figure not available: see fulltext.] © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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