Selenium inhibits ferroptosis in ulcerative colitis through the induction of Nrf2/Gpx4 - 25/09/24
, Shan Ji a, Mengyao Xu a, Yongan Wang b, Hui Shi a, ⁎ Highlights |
• | The serum selenium content of UC patients was lower than that of healthy subjects. In addition, serum selenium levels were negatively correlated with disease activity. |
• | Caco2 cell experiment showed that selenium could inhibit ferroptosis by up-regulating Nrf2/Gpx4 in Caco2 cells. |
• | The in vivo results showed that selenium treatment could improve IECs colitis induced by DSS and inhibit ferroptosis. |
Abstract |
Background and aim |
Selenium, an essential micronutrient for human and has been reported to have a protective effect in ulcerative colitis (UC). However, the role of selenium in UC is unclear. Our aim was to investigate the mechanism of action of selenium in UC.
Methods |
Serum selenium levels were measured in UC patients and healthy controls. In addition, the effect of sodium selenite supplementation on experimental colitis in mice treated with dextran sulfate sodium (DSS) was investigated. The effect of sodium selenite on IECs ferroptosis was evaluated by observing the cell mortality, intracellular ferrous content, lipid reactive oxygen species and mitochondrial membrane damage in DSS-treated Caco2 cells. In addition, glutathione peroxidase 4 (Gpx4) and nuclear factor erythroid 2-like 2 (Nrf2) were detected in Caco2 cells and mouse intestines to explore their mechanisms.
Results |
The serum selenium content of UC patients was lower than that of healthy subjects. In addition, serum selenium levels were negatively correlated with disease activity. The in vivo results showed that selenium treatment could improve colitis induced by DSS and inhibit IECs ferroptosis. The in vitro results further showed that selenium inhibited the ferroptosis of Caco-2 cells induced by DSS. Nrf2/Gpx4 was up-regulated after selenium supplementation in vivo and in vitro.
Conclusions |
Serum selenium level is associated with IECs ferroptosis in UC patients. Selenium can relieve DSS-induced colitis and inhibit IECs ferroptosis by up-regulating the expression of Nrf2/Gpx4.
Le texte complet de cet article est disponible en PDF.Keywords : Selenium, Nrf2, Gpx4, Ferroptosis, Colitis
Plan
Vol 48 - N° 9
Article 102467- novembre 2024 Retour au numéro
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