| First Author | Xie C | Year | 2014 |
| Journal | Int Immunopharmacol | Volume | 21 |
| Issue | 2 | Pages | 261-8 |
| PubMed ID | 24861250 | Mgi Jnum | J:318221 |
| Mgi Id | MGI:6858822 | Doi | 10.1016/j.intimp.2014.05.012 |
| Citation | Xie C, et al. (2014) Protective effect of SKLB010 against D-galactosamine/lipopolysaccharide-induced acute liver failure via nuclear factor-kappaB signaling pathway in macrophages. Int Immunopharmacol 21(2):261-8 |
| abstractText | Acute liver failure is characterized by the sudden loss of hepatic function and a high mortality. SKLB010, a derivative of thiazolidinediones, has been proved to be effective in protecting mice from acute liver failure caused by concanavalin A and carbon tetrachloride in our previous work. The purpose of the current study was to evaluate whether SKLB010 could prevent acute liver injury caused by d-galactosamine/lipopolysaccharide (LPS) in mice, and to investigate the underlying mechanisms. In the macrophage-mediated D-GalN/LPS model of acute liver injury, serum enzyme activity was suppressed and liver injury was attenuated by SKLB010. The serum levels of TNF-alpha and hepatic TNF-alpha mRNA expression were also markedly decreased after the treatment of SKLB010. In the liver of mice receiving injections of D-GalN/LPS, hepatocytes apoptosis and the infiltration of monocytes/macrophages were blocked by SKLB010. Furthermore, the survival rate of mice following D-GalN/LPS treatment was significantly improved by a single injection with SKLB010. In vivo, the luminescence intensity was suppressed by SKLB010 in NF-kappaB-luc mice after D-GalN/LPS treatment. In vitro, the production of tumor necrosis factor (TNF)-alpha and nitrite/nitrate in LPS-stimulated RAW264.7 macrophages was decreased by SKLB010 in a dose-dependent manner. Our further studies demonstrated that SKLB010 inhibited the phosphorylation of IkappaBalpha and p38MAPK, and the DNA binding activity of NF-kappaB in RAW264.7 cells. In conclusion, treatment with only a single injection of SKLB010 could significantly attenuate acute inflammation in mice induced by D-GalN/LPS, and these effects are likely associated with the inhibition of NF-kappaB activity. |
