The GSK3β inhibition by SB216763 ameliorates liver injury induced by D-GalN/LPS in C57BL/6 mice.
(a) Liver samples, harvested 6 h later, were subjected to Western blot analysis of phosphorylated glycogen synthases. Wild-type mice were pretreated with vehicle (DMSO, n = 3) or SB216763 (10, 25, 50 mg/kg, respectively, n = 3). Representative of one experiment is shown. Densitometry analysis of the proteins was performed for each sample (mean±SEM). (b)GSK3β inhibition enhances the survival rate of mice after D-GalN/LPS injection. SB216763 (10, 25, or 50 mg/kg body weight) or vehicle (DMSO) was intraperitoneally administered at 2 h before D-GalN/LPS injection (DMSO+D-GalN/LPS, SB216763 10 mg/kg+D-GalN/LPS, SB216763 25 mg/kg+D-GalN/LPS, SB216763 50 mg/kg+D-GalN/LPS); and the fifth group is administered SB216763 at 2 hour after D-GalN/LPS(D-GalN/LPS+SB216763 50 mg/kg). (n = 10/group). (c) Wild-type mice (n = 8–12) pretreated SB216763 before D-GalN/LPS injection were analyzed for serum ALT and AST level at 6 h after D-GalN/LPS. (d)Wild-type mice (n = 8–12) treated SB216763 after D-GalN/LPS injection were analyzed for serum ALT and AST level at 6 h after D-GalN/LPS. (e) Representative liver histology (H/E staining at 6 h after D-GalN/LPS) and the group averages of liver Suzuki scores (6 h). Control: DMSO groups, DMSO+D-GalN/LPS: model group, SB+D-GalN/LPS: prophylactic group and D-GalN/LPS+SB: therapeutic group. (n = 5–6/group).