Erythropoietin-induced cytoprotection in intestinal epithelial cells is linked to system Xc-

- System xC- is found in intestinal epithelial cells.
- S4-CPG and sulfasalazine inhibit system xC- causing cell death.
- Epo is protective against cell death in intestinal epithelial cells.
- Epo increases System xC- and causes cytoprotection.

Necrotizing enterocolitis is a common but serious complication among premature babies. Currently, there are limited treatment options. These include intensive supportive care and surgical intervention. In this study, we hypothesize that erythropoietin (Epo) could be protective against cell necrosis by increasing the levels of glutathione. This can be regulated by increasing the activity of system xC-. This was demonstrated using intestinal epithelial cells (IEC-6) as a model system. S4-CPG and sulfasalazine pharmacologically inhibit xCT, which induced cell death. Our data showed a dose dependent decrease in cell viability when treated with both inhibitors. In addition, the IEC-6 cells displayed a dose dependent increase when treated with Epo. In conclusion, Epo can be protective against cell death and ultimately be considered as a treatment option for intestinal epithelial cell death.