Micheliolide ameliorates lipopolysaccharide-induced acute kidney injury through suppression of NLRP3 activation by promoting mitophagy via Nrf2/PINK1/Parkin axis.
Int Immunopharmacol
; 138: 112527, 2024 Sep 10.
Article
in En
| MEDLINE
| ID: mdl-38950457
ABSTRACT
BACKGROUND:
Sepsis-associated acute kidney injury (SA-AKI) represents a frequent complication of in critically ill patients. The objective of this study is to illuminate the potential protective activity of Micheliolide (MCL) and its behind mechanism against SA-AKI.METHODS:
The protective potential of MCL on SA-AKI was investigated in lipopolysaccharide (LPS) treated HK2 cells and SA-AKI mice model. The mitochondrial damage was determined by detection of reactive oxygen species and membrane potential. The Nrf2 silencing was achieved by transfection of Nrf2-shRNA in HK2 cells, and Nrf2 inhibitor, ML385 was employed in SA-AKI mice. The mechanism of MCL against SA-AKI was evaluated through detecting hallmarks related to inflammation, mitophagy and Nrf2 pathway via western blotting, immunohistochemistry, and enzyme linked immunosorbent assay.RESULTS:
MCL enhanced viability, suppressed apoptosis, decreased inflammatory cytokine levels and improved mitochondrial damage in LPS-treated HK2 cells, and ameliorated renal injury in SA-AKI mice. Moreover, MCL could reduce the activation of NLRP3 inflammasome via enhancing mitophagy. Additionally, Nrf2 deficiency reduced the suppression effect of MCL on NLRP3 inflammasome activation and blocked the facilitation effect of MCL on mitophagy in LPS-treated HK2 cells, the consistent is true for ML385 treatment in SA-AKI mice.CONCLUSIONS:
MCL might target Nrf2 and further reduce the NLRP3 inflammasome activation via enhancing mitophagy, which alleviated SA-AKI.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Kinases
/
Sesquiterpenes, Guaiane
/
Ubiquitin-Protein Ligases
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NF-E2-Related Factor 2
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Acute Kidney Injury
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Mitophagy
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NLR Family, Pyrin Domain-Containing 3 Protein
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Int Immunopharmacol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Year:
2024
Document type:
Article
Country of publication:
Países Bajos