Crosstalk of TNF-α, IFN-γ, NF-kB, STAT1 and redox signaling in lipopolysaccharide/d-galactosamine/dimethylsulfoxide-induced fulminant hepatic failure in mice

Carfilzomib Mitigates Lipopolysaccharide/D-Galactosamine/Dimethylsulfoxide-Induced Acute Liver Failure in Mice

“…The present investigation demonstrated that the injection of LPS/GalN/DMSO led to a significant elevation in the activities of ALT and AST, consistent with the observations reported in prior studies [8,32]. The administration of various doses of CFZ one hour after the injection of LPS/GalN/DMSO resulted in a considerable reduction in ALT and AST levels in a dose-dependent manner.…”

“…The aforementioned impact was further investigated in order to elucidate its underlying mechanism of mitigation. The findings of our study agree with previous research, indicating a significant elevation in serum TNF-α levels among mice treated with LPS/GalN/DMSO [8,33,34]. The administration of CFZ following treatment with LPS/GalN/DMSO resulted in a considerable reduction in the increased levels of TNF-α as compared to the group treated with LPS/GalN/DMSO alone.…”

“…Carfilzomib (CFZ; Active Biochem, Maplewood, NJ, USA) was dissolved in DMSO and administered intraperitoneally 1 h after LPS/GalN/DMSO (Sigma-Aldrich, St. Louis, MO, USA) model. The final concentration of the CFZ solvent (DMSO) did not exceed 10 µL/kg which does not affect the model LPS/GalN/DMSO hepatotoxicity, as reported earlier [8]. LPS and GalN were dissolved in saline and administered intraperitoneally with DMSO directly after preparations at a dose of (10 µg/kg/400 mg/kg/200 µL/kg).…”

“…As GalN is only metabolized in liver cells, LPS/GalN induces programed cell death solely in hepatic cells [2]. Previous studies proved the toxic influence of dimethylsulfoxide (DMSO) on hepatic cells in vivo, as demonstrated by the elevated pro-inflammatory cytokines and exacerbating LPS/GalN-inducing ALF, which could afford an improved and useful animal model for ALF and inflammatory hepatic injury [7,8].…”

Signaling pathways of liver regeneration: Biological mechanisms and implications

“…TNF-α participates in numerous liver biological responses and exerts a critical effect on hepatitis, liver fibrosis, liver failure, and LR. 57 , 58 , 59 , 60 After PHx, TNF-α activates NF-κB by binding to TNFR-1, which translocates NF-κB into the nucleus and induces IL-6 expression, subsequently, IL-6 activates STAT3 to promote LR. 61 When TNF-α is blocked, the production of IL-6 and LR will be inhibited.…”