taurochenodeoxycholic-acid and Leukemia--Myeloid--Acute

The aim of this study is to investigate the protective effect and the mechanism of tauroursodeoxycholic acid (TUDCA) against hepatic ischemia reperfusion (IR) injury. Male Balb/c mice were intraperitoneally injected with tauroursodeoxycholic acid (400 mg/kg) or saline solution, once per day for 3 days before surgery, and then the model of hepatic I/R injury was established. Blood and liver samples were collected from each group at 3, 6, and 24 h after surgery. Liver pathological changes, liver function, hepatocyte apoptosis and proinflammatory factors were detected. KCs were extracted, cultured and treated with TUDCA or phosphate-buffered saline (PBS) for 24 h, and then viability and phagocytosis were examined. Additionally, IRE1α/TRAF2/NF-κB pathway activity and AML cell apoptosis were detected. The results showed that TUDCA alleviated hepatic I/R injury, the level of liver function markers, and hepatocyte apoptosis in vivo. Furthermore, the proinflammatory effects of KCs were suppressed by down-regulating IRE1α/TRAF2/NF-κB pathway activity in vivo. TUDCA dose-dependently suppressed the expression of inflammatory factors and IRE1α/TRAF2/NF-κB pathway activity in vitro, consistent with the in vivo results. Therefore, TUDCA can effectively alleviate hepatic IR injury by down-regulating the activity of the IRE1α/TRAF2/NF-κB pathway to suppress the function of KCs.

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Survival; Coculture Techniques; Cytokines; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Endoplasmic Reticulum Stress; Endoribonucleases; Inflammation Mediators; Kupffer Cells; Leukemia, Myeloid, Acute; Liver; Liver Diseases; Male; Mice, Inbred BALB C; NF-kappa B; Protein Serine-Threonine Kinases; Reperfusion Injury; Signal Transduction; Taurochenodeoxycholic Acid; Time Factors; TNF Receptor-Associated Factor 2