Serum metallomics of inflammation model mice and anti-inflammatory effects of selenium-containing compounds

<p>Inflammation is closely related to trace elements in blood, and selenium has been reported to be inversely correlated with COVID-19 severity. There is a close relationship between antioxidant and anti-inflammatory effects, and the selenium-containing antioxidant Ebselen suppresses the inflammatory response associated with influenza. Here we sought to identify target elements for suppressing inflammation by metallomics of LPS-treated mice and to develop new anti-inflammatory drugs focusing on selenium.Serum metallomics analysis of LPS-treated mice revealed a strong correlation between cytokine expression in the liver and changes in serum trace elements such as zinc, copper, selenium, and potassium. In addition, we found that inflammation decreased GPx1 expression in the liver and that high-dose LPS administration decreased serum selenium, suggesting that selenium may be a target for anti-inflammatory drugs. Using a coupling assay with hydrogen peroxide and lipid hydroperoxide, we measured the antioxidant activity of new selenium-containing compounds. We found 3 compounds with strong antioxidant activity. These compounds inhibited cell death induced by oxidative stresses. These compounds showed not only their own antioxidant activity but also induction of antioxidant factor GPx1. The antioxidant activity of compounds contributed to anti-inflammatory effects, and the expression of cytokines was reduced. In mice, these compounds also showed a tendency to suppress inflammation. In conclusion, these selenium compounds are the potential candidates for anti-inflammatory drugs.</p>