Bryostatin‐1 attenuates intestinal ischemia/reperfusion‐induced intestinal barrier dysfunction, inflammation, and oxidative stress via activation of Nrf2/HO‐1 signaling

Abstract

AbstractBryostatin‐1 (Bryo‐1) exerts antioxidative stress effects in multiple diseases, and we confirmed that it improves intestinal barrier dysfunction in experimental colitis. Nevertheless, there are few reports on its action on intestinal ischemia/reperfusion (I/R). In this study, we mainly explored the effect of Bryo‐1 on intestinal I/R injury and determined the mechanism. C57BL/6J mice underwent temporary superior mesenteric artery (SMA) obturation to induce I/R, on the contrary, Caco‐2 cells suffered to oxygen and glucose deprivation/reperfusion (OGD/R) to establish the in vitro model. RAW264.7 cells were stimulated with LPS to induce macrophage inflammation. The drug gradient experiment was used to demonstrate in vivo and in vitro models. Bryo‐1 ameliorated the intestinal I/R‐induced injury of multiple organs and epithelial cells. It also alleviated intestinal I/R‐induced barrier disruption of intestines according to the histology, intestinal permeability, intestinal bacterial translocation rates, and tight junction protein expression results. Bryo‐1 significantly inhibited oxidative stress damages and inflammation, which may contribute to the restoration of intestinal barrier function. Further, Bryo‐1 significantly activated Nrf2/HO‐1 signaling in vivo. However, the deletion of Nrf2 in Caco‐2 and RAW264.7 cells attenuated the protective functions of Bryo‐1 and significantly abolished the anti‐inflammatory effect of Bryo‐1 on LPS‐induced macrophage inflammation. Bryo‐1 protects intestines against I/R‐induced injury. It is associated with intestinal barrier protection, as well as inhibition of inflammation and oxidative stress partly through Nrf2/HO‐1 signaling.