Inhibition RIP1 prevents acute liver failure by suppressing hepatic apoptosis and attenuating the secretion of TNF-α from macrophages.

BACKGROUND AND AIMS: Acute liver failure (ALF) is a rapidly progressing clinical syndrome with a high mortality rate and limited treatment options. In this study, we used the RIP1 kinase inhibitor necrostatin-1 (Nec-1) to explore the effect and mechanism of RIP1 in lipopolysaccharide (LPS)/D-galactosamine (GalN)-induced ALF. RESULTS: Nec-1 pretreatment significantly ameliorated ALF, as evidenced by reduced hepatic necrosis and serum alanine aminotransferase levels. Additionally, Nec-1 administration alleviated LPS/GalN-induced hepatocyte apoptosis in liver tissues. Further in vitro experiments revealed that Nec-1 inhibited the secretion of TNF-α from macrophages and reduced TNF-α-induced hepatocyte apoptosis. CONCLUSIONS: Inhibition of RIP1 effectively alleviated LPS/GalN-induced ALF by reducing hepatic apoptosis and attenuating the secretion of TNF-α from macrophages, suggesting its potential as a therapeutic agent for ALF patients.