Bazedoxifene attenuates intestinal injury in sepsis by suppressing the NF-κB/NLRP3 signaling pathways.
Eur J Pharmacol
; 947: 175681, 2023 May 15.
Article
in En
| MEDLINE
| ID: mdl-36965746
ABSTRACT
Acute inflammatory injury is the primary cause of sepsis, leading to various organ failures. Bazedoxifene (BAZ) has been proven to have anti-inflammatory effects. However, its effects on sepsis-induced intestinal injury are unclear. Here, we demonstrated the beneficial effects of BAZ on intestinal injury and explored the underlying mechanisms using cecal ligation and perforation (CLP)-mediated sepsis mouse model and in vitro cultured intestinal epithelial MODE-K cells. We found that BAZ elevated the survival rate of septic mice and attenuated CLP-triggered intestinal damage. BAZ inhibited intestinal inflammation and restored the impaired intestinal barriers in CLP mice. The mechanistic study in lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-stimulated MODE-K cells showed that BAZ significantly downregulated the expression of NOD-like receptor protein 3 (NLRP3), interleukin-1ß (IL-1ß), caspase-1, and gasdermin D (GSDMD), and markedly reduced the phosphorylation of molecules in the nuclear factor kappa B (NF-κB) pathway. Moreover, BAZ prominently rescued the decreased viability of MODE-K cells and reduced lactate dehydrogenase (LDH) release upon LPS/ATP challenge. However, BAZ did not affect the inflammasome assembly, as evidenced by the lack of changes in ASC (apoptosis speck-like protein containing a CARD) speck formation. Our results suggest that BAZ relieves inflammation and intestinal barrier function disruption by suppressing the NF-κB/NLRP3 signaling pathways. Therefore, BAZ is a potential therapeutic candidate for treating intestinal injury in sepsis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
NF-kappa B
/
Sepsis
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Eur J Pharmacol
Year:
2023
Document type:
Article
Affiliation country:
China