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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| Language: | English |
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BMC
2025-07-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02948-y |
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| author | Aichun Li Dahua Chen Jianwei Shen |
| author_facet | Aichun Li Dahua Chen Jianwei Shen |
| author_sort | Aichun Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e99a13f1130540ca80e7b331e272b851 |
| institution | DOAJ |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-e99a13f1130540ca80e7b331e272b8512025-08-20T03:04:31ZengBMCEuropean Journal of Medical Research2047-783X2025-07-013011710.1186/s40001-025-02948-yInhibition RIP1 prevents acute liver failure by suppressing hepatic apoptosis and attenuating the secretion of TNF-α from macrophagesAichun Li0Dahua Chen1Jianwei Shen2Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo UniversityDepartment of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo UniversityDepartment of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo UniversityAbstract 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.https://doi.org/10.1186/s40001-025-02948-yAcute liver failureRIP1ApoptosisTNF-αMacrophages |
| spellingShingle | Aichun Li Dahua Chen Jianwei Shen Inhibition RIP1 prevents acute liver failure by suppressing hepatic apoptosis and attenuating the secretion of TNF-α from macrophages European Journal of Medical Research Acute liver failure RIP1 Apoptosis TNF-α Macrophages |
| title | Inhibition RIP1 prevents acute liver failure by suppressing hepatic apoptosis and attenuating the secretion of TNF-α from macrophages |
| title_full | Inhibition RIP1 prevents acute liver failure by suppressing hepatic apoptosis and attenuating the secretion of TNF-α from macrophages |
| title_fullStr | Inhibition RIP1 prevents acute liver failure by suppressing hepatic apoptosis and attenuating the secretion of TNF-α from macrophages |
| title_full_unstemmed | Inhibition RIP1 prevents acute liver failure by suppressing hepatic apoptosis and attenuating the secretion of TNF-α from macrophages |
| title_short | Inhibition RIP1 prevents acute liver failure by suppressing hepatic apoptosis and attenuating the secretion of TNF-α from macrophages |
| title_sort | inhibition rip1 prevents acute liver failure by suppressing hepatic apoptosis and attenuating the secretion of tnf α from macrophages |
| topic | Acute liver failure RIP1 Apoptosis TNF-α Macrophages |
| url | https://doi.org/10.1186/s40001-025-02948-y |
| work_keys_str_mv | AT aichunli inhibitionrip1preventsacuteliverfailurebysuppressinghepaticapoptosisandattenuatingthesecretionoftnfafrommacrophages AT dahuachen inhibitionrip1preventsacuteliverfailurebysuppressinghepaticapoptosisandattenuatingthesecretionoftnfafrommacrophages AT jianweishen inhibitionrip1preventsacuteliverfailurebysuppressinghepaticapoptosisandattenuatingthesecretionoftnfafrommacrophages |