Terlipressin protects intestinal epithelial cells against oxygen-glucose deprivation/re-oxygenation injury via the phosphatidylinositol 3-kinase pathway.

Intestinal ischemia/reperfusion (I/R) injury is associated with a high morbidity and mortality. Vasopressin is administered to critically ill patients with potential intestinal I/R. However, the impacts of vasopressin on intestinal epithelia under ischemic/anoxic conditions remain unclear. The aim of the present study was to evaluate the effects of terlipressin, a highly selective vasopressin V1 receptor agonist, on oxygen and glucose deprivation/re-oxygenation (OGD/R)-induced damage in intestinal epithelial cells (IEC-6). IEC-6 cells were subjected to OGD for 4 h, followed by 4 h re-oxygenation. Terlipressin was incubated with cells for 4 h following OGD. Following OGD/R, IEC-6 cell viability, proliferation and apoptosis, as well as cell cycle dynamics, were assessed and the levels of tumor necrosis factor (TNF)-α and 15-F2t-isoprostane in the culture medium were measured. In addition, wortmannin, a specific phosphatidylinositol 3-kinase (PI3K) inhibitor, was administrated to investigate the mechanism of terlipressin action. The results demonstrated that IEC-6 cell viability and proliferation decreased, and cell apoptosis increased, following OGD/R. However, IEC-6 cell cycle dynamics did not significantly change 4 h after OGD. Incubation with 25 nM terlipressin significantly improved cell viability, proliferation and apoptosis. Furthermore, terlipressin inhibited the secretion of TNF-α and 15-F2t-isoprostane from IEC-6 cells following OGD/R. The aforementioned effects of terlipressin were completely abolished following the application of 2 µM wortmannin. Therefore, the current study demonstrated that terlipressin administration following OGD attenuates OGD/R-induced cell damage via the PI3K signaling pathway. These results may help physicians to better understand and more effectively use terlipressin in a clinical setting.