Arsenic retention in erythrocytes and excessive erythrophagocytosis is related to low selenium status by impaired redox homeostasis.

Arsenic (As) contamination in drinking water is a global public health problem. Epidemiological studies have shown that selenium (Se) deficiency is associated with an increasing risk of arsenism. However, the association between Se status and As retention in erythrocytes and mechanisms underlying this association have not been fully investigated. In the present study, a total of 165 eligible subjects were recruited and As was found to accumulate in blood mainly by retention in erythrocytes. Retention of As in erythrocytes was negatively correlated with Se status, antioxidant parameters related to Se and As methylation capacity, but positively correlated with the protein-binding capacity of As. Additionally, erythrocytes isolated from subjects with low Se status exhibited cellular damage along with lower protein levels of CD47, which could be aggravated by hydrogen peroxide treatment. Consistent with the human study, the erythrocytes from mice with sub-chronic As exposure exhibited similar cellular damage and shown to be phagocytosed by splenic macrophages, and these effects were mitigated by dietary Se supplementation. Furthermore, hydrogen peroxide treatment induced excessive phagocytosis of erythrocytes with As exposure by splenic macrophages, while co-treating erythrocytes with the reducing agent, N-Acetyl-l-cysteine, mitigated this excessive erythrophagocytosis. Hyperactivation of the NFκB pathway was also detected in splenic macrophages after excessive erythrophagocytosis. In conclusion, this study found that low Se status involving impaired redox homeostasis increased As retention in erythrocytes, which were subsequently phagocytosed by splenic macrophages and led to an increased inflammatory status of splenic macrophages. These findings provide insight into physiological features of arsenism related to Se status and redox homeostasis.

Methylseleninic Acid Provided at Nutritional Selenium Levels Inhibits Angiogenesis by Down-regulating Integrin ß3 Signaling.

Targeting angiogenesis has emerged as a promising strategy for cancer treatment. Methylseleninic acid (MSA) is a metabolite of selenium (Se) in animal cells that exhibits anti-oxidative and anti-cancer activities at levels exceeding Se nutritional requirements. However, it remains unclear whether MSA exerts its effects on cancer prevention by influencing angiogenesis within Se nutritional levels. Herein, we demonstrate that MSA inhibited angiogenesis at 2 µM, which falls in the range of moderate Se nutritional status. We found that MSA treatments at 2 µM increased cell adherence, while inhibiting cell migration and tube formation of HUVECs in vitro. Moreover, MSA effectively inhibited the sprouts of mouse aortic rings and neoangiogenesis in chick embryo chorioallantoic membrane. We also found that MSA down-regulated integrin ß3 at the levels of mRNA and protein, and disrupted clustering of integrin ß3 on the cell surface. Additionally, results showed that MSA inhibited the phosphorylation of AKT, IκBα, and NFκB. Overall, our results suggest that exogenous MSA inhibited angiogenesis at nutritional Se levels not only by down-regulating the expression of integrin ß3 but also by disorganizing the clustering of integrin ß3, which further inhibited the phosphorylation involving AKT, IκBα, NFκB. These findings provide novel mechanistic insight into the function of MSA for regulating angiogenesis and suggest that MSA could be a potential candidate or adjuvant for anti-tumor therapy in clinical settings.

Selenium nanoparticles decorated with Ulva lactuca polysaccharide potentially attenuate colitis by inhibiting NF-κB mediated hyper inflammation.

BACKGROUND: Selenium (Se) is an essential micronutrient trace element and an established nutritional antioxidant. Low Se status exacerbates inflammatory bowel diseases progression, which involves hyper inflammation in the digestive tract. Se nanoparticles (SeNPs) exhibit anti-inflammatory activity accompanied by low toxicity, especially when decorated with natural biological compounds. Herein, we explored the beneficial effects of SeNPs decorated with Ulva lactuca polysaccharide (ULP) in mice subjected to the acute colitis model. RESULTS: We constructed SeNPs coated with ULP (ULP-SeNPs) in average diameter ~130 nm and demonstrated their stability and homogeneity. Supplementation with ULP-SeNPs (0.8 ppm Se) resulted in a significant protective effect on DSS-induced acute colitis in mice including mitigation of body weight loss, and colonic inflammatory damage. ULP-SeNPs ameliorated macrophage infiltration as evidenced by decreased CD68 levels in colon tissue sections. The anti-inflammatory effects of ULP-SeNPs were found to involve modulation of cytokines including IL-6 and TNF-α. Mechanistically, ULP-SeNPs inhibited the activation of macrophages by suppressing the nuclear translocation of NF-κB, which drives the transcription of these pro-inflammatory cytokines. CONCLUSIONS: ULP-SeNPs supplementation may offer therapeutic potential for reducing the symptoms of acute colitis through its anti-inflammatory actions.

Selenium-Containing Phycocyanin from Se-Enriched Spirulina platensis Reduces Inflammation in Dextran Sulfate Sodium-Induced Colitis by Inhibiting NF-κB Activation.

Selenium (Se) plays an important role in fine-tuning immune responses. Inflammatory bowel disease (IBD) involves hyperresponsive immunity of the digestive tract, and a low Se level might aggravate IBD progression; however, the beneficial effects of natural Se-enriched diets on IBD remain unknown. Previously, we developed high-yield Se-enriched Spirulina platensis (Se-SP) as an excellent organic nutritional Se source. Here we prepared Se-containing phycocyanin (Se-PC) from Se-SP and observed that Se-PC administration effectively reduced the extent of colitis in mouse induced by dextran sulfate sodium. Supplementation with Se-PC resulted in significant protective effects, including mitigation of body weight loss, bloody diarrhea, and colonic inflammatory damage. The anti-inflammatory effects of Se-PC supplementation were found to involve modulation of cytokines, including IL-6, TNF-α, MCP-1, and IL-10. Mechanistically, Se-PC inhibited the activation of macrophages by suppressing the nuclear translocation of NF-κB, which is involved in the transcription of these pro-inflammatory cytokines. These results together suggest potential benefits of Se-PC as a functional Se supplement to reduce the symptoms of IBD.