Synthetic RGDS peptide attenuated lipopolysaccharide/D-galactosamine-induced fulminant hepatic failure in mice

Background and aim: Fulminant hepatic failure (FHF) is a serious clinic syndrome with extremely poor prognosis and no effective treatment except for liver transplantation. Synthetic RGDS peptide, an inhibitor of integrins, was proved to suppress Integrin signals. In this study, we investigated the protection effects of RGDS peptide on lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced FHF and the underlying molecular mechanisms.

Methods: Synthetic RGDS peptide was given intraperitoneally 30 min before LPS/D-GalN injection. Liver function and the extent of liver injury were analyzed biochemically and pathologically respectively. Enzyme-linked immunosorbent assay, real-time polymerase chain reaction and Western blotting were used to detect effectors and signaling molecules.

Results: Pretreatment with synthetic RGDS peptide significantly improved LPS/D-GalN-induced mortality, and liver injury as determined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, as well as pathological analysis. In addition, RGDS peptide significantly reduced tumor necrosis factor (TNF)-α and macrophage inflammatory protein (MIP)-2 production, and decreased myeloperoxidase (MPO) and NF-κB activity. Furthermore, Western blotting indicated that the levels of phospho-integrin β3, phospho-focal adhesion kinase (FAK) and phospho-p38 mitogen-activated protein kinases (MAPK) decreased with RGDS peptide pretreatment.

Conclusion: Together, these data suggest that synthetic RGDS peptide protect against LPS/D-GalN-induced FHF by inhibiting inflammatory cells migration and blocking the Integrin αVβ3-FAK-p38 MAPK and NF-κB signaling.