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

Abstract 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...

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Bibliographic Details
Published in:European Journal of Medical Research
Main Authors: Aichun Li, Dahua Chen, Jianwei Shen
Format: Article
Language:English
Published: BMC 2025-07-01
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Online Access:https://doi.org/10.1186/s40001-025-02948-y
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Summary:Abstract 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.
ISSN:2047-783X