Selenium alleviates dextran sulfate sodium‐induced colitis and inhibits ferroptosis of intestinal epithelial cells via upregulating glutathione peroxidase 4.

Background and Aim Methods Results Conclusions Selenium, an essential micronutrient for humans, has been shown to be protective against ulcerative colitis (UC), but the exact mechanism remains unclear. The role of selenium, protecting against ferroptosis of intestinal epithelial cells (IECs) in colitis, was investigated in this current study.Serum selenium level and ferroptosis‐related gene expression in the colonic mucosa were measured in UC patients and healthy controls. The effects of sodium selenite supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)‐treated mice. The influence of sodium selenite on IEC ferroptosis was evaluated through assessing cell death rate, intracellular ferrous iron content, lipid reactive oxygen species level, and mitochondrial membrane damage of DSS‐treated Caco‐2 cells. Moreover, glutathione peroxidase 4 (GPX4) and acyl‐CoA synthetase long‐chain family member 4, ferroptosis‐related genes, were detected in Caco‐2 cells and mouse intestines.Serum selenium was decreased in UC patients in comparison with healthy individuals. Additionally, serum selenium level was negatively correlated with disease activity and was associated with clinical inflammation and nutrition indicators. The expression of GPX4 in the mucosa of UC was positively correlated with serum selenium level. The <italic>in vivo</italic> experiments showed that selenium treatment ameliorated DSS‐induced colitis and inhibited ferroptosis in IECs. The <italic>in vitro</italic> results suggested that selenium supplementation inhibited DSS‐induced ferroptosis in Caco‐2 cells. GPX4 was upregulated after selenium supplementation both <italic>in vivo</italic> and <italic>in vitro</italic>.Serum selenium level was associated with IEC ferroptosis in UC patients. Selenium supplementation alleviates DSS‐induced colitis and inhibits ferroptosis in IECs by upregulating the expression of GPX4. [ABSTRACT FROM AUTHOR]