Highlights
- •Cardiovascular disease prevalence has been rising more rapidly worldwide.
- •Low-grade systemic inflammation is well known as an independent cardiovascular risk factor.
- •Pyroptosis is characterized by release of pro-inflammatory cytokines including IL-1β and IL-18.
- •Selenium may exert beneficial actions for attenuating inflammation.
Abstract
Background and aims
Atherosclerosis as a chronic inflammatory disorder of the arterial wall is the main
leading cause of the cardiovascular disease (CVD). Caspase-dependent pyroptosis plays
a pivotal role in the pathogenesis of CVD. Selenium (Se) is an important component
of the antioxidant defense and plays a crucial role in cardiovascular health. This
study aimed to investigate the effects of daily consumption of sodium selenite and
Se-enriched yeast on the expression of pyroptosis-related genes, and biomarkers of
oxidative stress in patients with atherosclerosis.
Methods and results
In this randomized, double-blinded, placebo-controlled clinical trial, 60 patients
with atherosclerosis were recruited. Participants received 200 μg/day of sodium selenite,
Se-enriched yeast, or placebo for 8 following weeks. The pyroptosis-related genes’
mRNA expression in peripheral blood mononuclear cells (PBMCs) was assessed before
and after the intervention. Also, the levels of superoxide dismutase (SOD), malondialdehyde
(MDA), nitric oxide (NO), and glutathione peroxidases (GPX) were measured at baseline
and following the intervention. Following sodium selenite and Se-enriched yeast supplementation,
the relative expression levels of TLR4, ASC, NLRP3, and NF-κB1 were significantly
downregulated (p < 0.05). Furthermore, the changes in GPX were significantly increased
after selenite and yeast supplementation (p < 0.05). Also, selenite and yeast consumption
caused a statistically significant decrease in the change of MDA level (p < 0.05).
Conclusion
In summary, these findings showed that Se supplementation may reduce inflammation
through down-regulation of some pro-inflammatory genes, improving antioxidant defenses
in atherosclerosis patients. Further research is required to come to a definite conclusion
of selenium supplementation on the CVD risk.
This study was registered on the Iranian Registry of Clinical Trials website (identifier:
RCT20110123005670N28; https://www.irct.ir/).
Graphical abstract

Graphical Abstract
Keywords
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References
- Inflammatory cells in perivascular adipose tissue and the integrity of the tunica media in atherosclerotic coronary arteries.Bosn J Basic Med Sci. 2020; 20: 183-187
- A novel association between TGFb1 and ADAMTS4 in coronary artery disease: a new potential mechanism in the progression of atherosclerosis and diabetes.Anatol J Cardiol. 2015; 15: 823-829
- Research progress on the relationship between atherosclerosis and inflammation.Biomolecules. 2018; 8
- Redox regulation of cardiovascular inflammation - immunomodulatory function of mitochondrial and Nox-derived reactive oxygen and nitrogen species.Free Radic Biol Med. 2017; 109: 48-60
- Cytotoxicity and interleukin-1beta processing following Shigella flexneri infection of human monocyte-derived dendritic cells.Eur J Immunol. 2002; 32: 1464-1471
- NLRP3 inflammasome activation-mediated pyroptosis aggravates myocardial ischemia/reperfusion injury in diabetic rats.Oxid Med Cell Longev. 2017; (2017): 9743280
- Role of pyroptosis in cardiovascular diseases.Int Immunopharm. 2019; 67: 311-318
- Effects of oral butyrate and inulin supplementation on inflammation-induced pyroptosis pathway in type 2 diabetes: a randomized, double-blind, placebo-controlled trial.Cytokine. 2020; 131: 155101
- Role of pyroptosis in cardiovascular disease.Cell Prolif. 2019; 52: e12563
- Pyroptosis: a pro-inflammatory type of cell death in cardiovascular disease.Clin Chim Acta. 2020; 510: 62-72
- Role of pyroptosis in cardiovascular diseases and its therapeutic implications.Int J Biol Sci. 2019; 15: 1345
- Cutting edge: proteolytic inactivation of poly(ADP-ribose) polymerase 1 by the Nlrp3 and Nlrc4 inflammasomes.J Immunol. 2010; 185: 3127-3130
- Multifactorial activation of NLRP3 inflammasome: relevance for a precision approach to atherosclerotic cardiovascular risk and disease.Int J Mol Sci. 2020; 21
- NLRP3 activation induced by neutrophil extracellular traps sustains inflammatory response in the diabetic wound.Clin Sci (Lond). 2019; 133: 565-582
- Vascular inflammation and oxidative stress: major triggers for cardiovascular disease.Oxid Med Cell Longev. 2019; (2019): 7092151
- Effects of selenium supplementation on cardiovascular disease incidence and mortality: secondary analyses in a randomized clinical trial.Am J Epidemiol. 2006; 163: 694-699
- Serum levels OF tnf-a, IL-6, selenium, zinc, and copper IN patients with acute and chronic coronary artery disease.IRANIAN JOURNAL OF IMMUNOLOGY (IJI), 2006
- Selenium in human health and disease.Antioxidants Redox Signal. 2011; 14: 1337-1383
- Selenium and its supplementation in cardiovascular disease--what do we know?.Nutrients. 2015; 7: 3094-3118
- Serum selenium levels and oxidative balance as differential markers in hepatic damage caused by alcohol.Life Sci. 2014; 94: 158-163
- Effects of dietary selenium, vitamin E, and their combination on growth, serum metabolites, and antioxidant defense system in skeletal muscle of broilers under heat stress.Biol Trace Elem Res. 2012; 148: 322-330
- The influence of selenium-enriched milk proteins and selenium yeast on plasma selenium levels and rectal selenoprotein gene expression in human subjects.Br J Nutr. 2011; 106: 572-582
- Preparation of selenium yeasts I. Preparation of selenium-enriched Saccharomyces cerevisiae.J Trace Elem Med Biol. 2000; 14: 43-47
- Effect of supplementation with high-selenium yeast on plasma lipids: a randomized trial.Ann Intern Med. 2011; 154: 656-665
- Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method.Methods. 2001; 25: 402-408
- The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review).Vasc Pharmacol. 2015; 71: 40-56
- The importance OF selenium and zinc deficiency IN cardiovascular disorders.Environmental Toxicology and Pharmacology, 2020: 103553
- Progress in the emerging role of selenoproteins in cardiovascular disease: focus on endoplasmic reticulum-resident selenoproteins.Cell Mol Life Sci. 2019; 76: 3969-3985
- Seleno-enzymes and seleno-compounds: the two faces of selenium.Crit Care. 2006; 10: 1-2
- Serum selenium and glutathione peroxidase-3 activity: biomarkers of systemic inflammation in the critically ill?.Intensive Care Med. 2009; 35: 882-889
- Interference of selenium and selenoproteins with the insulin-regulated carbohydrate and lipid metabolism.Free Radic Biol Med. 2013; 65: 1538-1547
- Effects of vitamin E and selenium yeast on growth performance and immune function in ducks fed maize naturally contaminated with aflatoxin B1.Livest Sci. 2013; 152: 200-207
- Ukrainian dietary bakery product with selenium-enriched yeast.LWT-food Science and Technology. 2008; 41: 890-895
- Improved antioxidant capacity and immune function of broiler chickens fed with selenium-enriched Candida utilis.Brazilian Journal of Poultry Science. 2020; 22
- Influences of selenium-enriched yeast on growth performance, immune function, and antioxidant capacity in weaned pigs exposure to oxidative stress.BioMed Res Int. 2021; (2021)
- NLRP3 inflammasome: a new pharmacological target for reducing testicular damage associated with varicocele.Int J Mol Sci. 2021; 22: 1319
- Anti-inflammatory effect of selenium on lead-induced testicular inflammation by inhibiting NLRP3 inflammasome activation in chickens.Theriogenology. 2020; 155: 139-149
- Dietary selenium supplementation alleviates immune toxicity in the hearts of chickens with lead-added drinking water.Avian Pathol. 2019; 48: 230-237
- NLRP3 inflammasome is involved in the mechanism of mitigative effect of selenium on lead-induced inflammatory damage in chicken kidneys.Environ Sci Pollut Control Ser. 2021; 28: 10898-10908
- Effect of selenium on testicular damage induced by varicocele in adult male Wistar rats.J Trace Elem Med Biol. 2017; 44: 177-185
- Selenium-related nutritional status in patients with common variable immunodeficiency: association with oxidative stress and atherosclerosis risk.BMC Immunol. 2021; 22: 1-8
- Selenium deficiency facilitates inflammation through the regulation of TLR4 and TLR4-related signaling pathways in the mice uterus.Inflammation. 2015; 38: 1347-1356
- Curcumin and selenium prevent lipopolysaccharide/diclofenac-induced liver injury by suppressing inflammation and oxidative stress.Biol Trace Elem Res. 2020; 196: 173-183
- Effects of selenium supplementation on metabolic status in patients undergoing for coronary artery bypass grafting (CABG) surgery: a randomized, double-blind, placebo-controlled trial.Biol Trace Elem Res. 2019; 191: 331-337
- Selenium-rich-yeast protects against aluminum-induced activating nuclear xenobiotic receptors and triggering inflammation and cytochromes P450 systems in mice heart.Biol Trace Elem Res. 2020; 194: 244-250
- MicroRNA-223 triggers inflammation in porcine aorta by activating NLRP3 inflammasome under selenium deficiency.J Cell Physiol. 2021; 236: 4555-4564
- Selenium supplementation lowers insulin resistance and markers of cardio-metabolic risk in patients with congestive heart failure: a randomised, double-blind, placebo-controlled trial.Br J Nutr. 2018; 120: 33-40
- Effects of chemical form of selenium on plasma biomarkers in a high-dose human supplementation trial.Cancer Epidemiology and Prevention Biomarkers. 2006; 15: 804-810
- Evaluating the efficacy of selenium-enriched yeast and sodium selenite on tissue selenium retention and serum glutathione peroxidase activity in grower and finisher swine.J Anim Sci. 1996; 74: 2967-2974
Article info
Publication history
Published online: March 07, 2022
Accepted:
February 21,
2022
Received in revised form:
February 5,
2022
Received:
September 27,
2021
Handling Editor: A. NaskaIdentification
Copyright
© 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.