Selective Impact of Selenium Compounds on Two Cytokine Storm Players

Sinha et al., Preprints, doi:10.20944/preprints202308.1168.v1

Aug 2023

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In Vitro analysis of selenium for reducing inflammatory cytokine production in a cell model of COVID-19 infection. Methylseleninic acid was the most potent at reducing secretion of the cytokines IL-6 and TNF-α, key factors in the cytokine storm in severe COVID-19. Authors also show an increase in Nrf2 and decrease in pIkBa in human macrophages with methylseleninic acid.

3 preclinical studies support the efficacy of selenium for COVID-19:

2 In Vitro studies1,2

1 In Vivo animal study3

Selenium has been identified by the European Food Safety Authority (EFSA) as having sufficient evidence for a causal relationship between intake and optimal immune system function4-6. Selenium may be beneficial for COVID-19 by inhibiting ferroptosis, an oxidative stress-induced cell death pathway implicated in COVID-19 pathogenesis7. Selenium enhances immune response, inhibits ROS production, and protects against ferroptosis via GPX4 induction8.

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1. Sinha et al., Selective Impact of Selenium Compounds on Two Cytokine Storm Players, Preprints, doi:10.20944/preprints202308.1168.v1.preprints.org, doi.org.

2. Hajdrik et al., In Vitro Determination of Inhibitory Effects of Humic Substances Complexing Zn and Se on SARS-CoV-2 Virus Replication, Foods, doi:10.3390/foods11050694.mdpi.com, doi.org.

3. Zhou et al., Metal-coding assisted serological multi-omics profiling deciphers the role of selenium in COVID-19 immunity, Chemical Science, doi:10.1039/d3sc03345g.rsc.org, doi.org.

4. Galmés et al., Suboptimal Consumption of Relevant Immune System Micronutrients Is Associated with a Worse Impact of COVID-19 in Spanish Populations, Nutrients, doi:10.3390/nu14112254.mdpi.com, doi.org.

5. Galmés (B) et al., Current State of Evidence: Influence of Nutritional and Nutrigenetic Factors on Immunity in the COVID-19 Pandemic Framework, Nutrients, doi:10.3390/nu12092738.mdpi.com, doi.org.

6. EFSA, Scientific Opinion on the substantiation of health claims related to selenium and protection of DNA, proteins and lipids from oxidative damage (ID 277, 283, 286, 1289, 1290, 1291, 1293, 1751), function of the immune system (ID 278), thyroid function (ID 279, 282, 286, 1289, 1290, 1291, 1293), function of the heart and blood vessels (ID 280), prostate function (ID 284), cognitive function (ID 285) and spermatogenesis (ID 396) pursuant to Article 13(1) of Regulation (EC) No 1924/2006, EFSA Journal, doi:10.2903/j.efsa.2009.1220.europa.eu, doi.org.

7. Yuan et al., The role of cell death in SARS-CoV-2 infection, Signal Transduction and Targeted Therapy, doi:10.1038/s41392-023-01580-8.nature.com, doi.org.

8. Xie et al., The role of reactive oxygen species in severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection-induced cell death, Cellular & Molecular Biology Letters, doi:10.1186/s11658-024-00659-6.biomedcentral.com, doi.org.

Sinha et al., 16 Aug 2023, preprint, 3 authors. Contact: rsinha@pennstatehealth.psu.edu (corresponding author), isinha@pennstatehealth.psu.edu, jzhu2@pennstatehealth.psu.edu.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

This Paper Selenium All

Selective Impact of Selenium Compounds on Two Cytokine Storm Players

Indu Sinha, Junjia Zhu, Raghu Sinha

doi:10.20944/preprints202308.1168.v1

COVID-19 patients suffer from detrimental effects of cytokine storm and not much success has been achieved to overcome this issue. We sought to test the ability of selenium in reducing the impact of two important cytokine storm players; IL-6 and TNF-. The effects of four selenium compounds were evaluated on the secretion of these cytokines from THP-1 macrophages in vitro following LPS challenge. Also, potential impact of methylseleninic acid (MSeA) on Nrf2 and IB was determined following short treatment of THP-1 macrophages. MSeA was observed to be the most potent selenium form to reduce IL-6 and TNF- levels among the four selenium compounds tested. In addition, an increase in Nrf2 and decrease in pIB in human macrophages was observed following MSeA treatment. Our data indicate that COVID-19 patients might benefit by suppressing their cytokine storm with addition of MSeA to the standard therapy.

Supplementary Materials: Not applicable Author Contributions: Conceptualization, I.S. and R.S.; methodology, I.S.; validation, I.S. and R.S.; formal analysis, I.S., J.Z. and R.S.; investigation, I.S.; writing-original draft preparation, R.S.; writing-review and editing, I.S., J.Z. and R.S.; visualization, I.S. and R.S.; supervision, R.S.; project administration, R.S. All authors have read and agreed to the published version of the manuscript. Conflicts of Interest: The authors declare no conflict of interest.

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