Organic Selenium Reaches the Central Nervous System and Downmodulates Local Inflammation: A Complementary Therapy for Multiple Sclerosis?

Abstract

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). The persistent inflammation is being mainly attributed to local oxidative stress and inflammasome activation implicated in the ensuing demyelination and axonal damage. Since new control measures remain necessary, we evaluated the preventive and therapeutic potential of a beta-selenium-lactic acid derivative (LAD-bSe), which is a source of organic selenium under development, to control experimental autoimmune encephalomyelitis (EAE) that is an animal model for MS. Two EAE murine models: C57BL/6 and SJL/J immunized with myelin oligodendrocyte glycoprotein and proteolipid protein, respectively, and a model of neurodegeneration induced by LPS in male C57BL/6 mice were used. The preventive potential of LAD-bSe was initially tested in C57BL/6 mice, the chronic MS model, by three different protocols that were started 14 days before or 1 or 7 days after EAE induction and were extended until the acute disease phase. These three procedures were denominated preventive therapy −14 days, 1 day, and 7 days, respectively. LAD-bSe administration significantly controlled clinical EAE development without triggering overt hepatic and renal dysfunction. In addition of a tolerogenic profile in dendritic cells from the mesenteric lymph nodes, LAD-bSe also downregulated cell amount, activation status of macrophages and microglia, NLRP3 (NOD-like receptors) inflammasome activation and other pro-inflammatory parameters in the CNS. The high Se levels found in the CNS suggested that the product crossed the blood-brain barrier having a possible local effect. The hypothesis that LAD-bSe was acting

Selenium metabolism and regulation of immune cells in immune‐associated diseases

“…According to existing results, selenium affects subsets of DCs to change later immune response. It has been showed that preventive selenium supplement 1 day after experimental autoimmune encephalomyelitis induction (45 μg Se/day till the acute disease phase) can reduce the proportion of activated DCs (CD11c + MHCII + ) while increase tolerogenic DCs (CD11b ‐ CD103 + ) (de Toledo et al, 2020). As late selenium supplement (7 days after disease inducement) can't help suppress disease process, this change can help downregulate local inflammation in a preventative way.…”

Stress and the Brain: An Emerging Role for Selenium

“…Insufficient selenium supply and lack of selenoprotein function have been linked to multiple brain disorders, including neurodegenerative diseases, which have been thoroughly discussed in previous reviews (Pillai et al, 2014;Solovyev, 2015;Varikasuvu et al, 2019;Zhang et al, 2019). Conversely, selenium has been suggested as a potential therapeutic agent in the treatment of Alzheimer's disease (Solovyev et al, 2018), multiple sclerosis (de Toledo et al, 2020), and stroke (Alim et al, 2019).…”

“…In a 2018 report, Sousa et al described the ability of the selenocompound α-(phenylselanyl) acetophenone (PSAP) to counteract the effects of ARS (Sousa et al, 2018). Previous studies demonstrated that PSAP has GPx-like antioxidant activity (Cotgreave et al, 1992) and antidepressant-like capabilities in mice (Gerzson et al, 2012). Sousa and colleagues immobilized mice in a restraint device for 4 h, followed by a battery of behavioral tests 40 min later.…”

Contribution of Metabolomics to Multiple Sclerosis Diagnosis, Prognosis and Treatment

“…The authors explained such a correlation considering that glutamine acts as a precursor to glutathione (GSH), GSH is a cofactor of glutathione-peroxidase (GSH-Px) and selenium is a prerequisite for the activity of GSH-Px that lowers the formation of reactive oxygen species (ROS) [60]. These results suggest that selenium may be a useful element in the treatment of MS [61].…”