SKLB023 protects against inflammation and apoptosis in sepsis-associated acute kidney injury via the inhibition of toll-like receptor 4 signaling.
Int Immunopharmacol
; 139: 112668, 2024 Sep 30.
Article
em En
| MEDLINE
| ID: mdl-39008938
ABSTRACT
Sepsis-associated acute kidney injury (SA-AKI) is one of common critical illnesses with high morbidity and mortality. At present, effective therapeutic drugs for SA-AKI are remain lacking. SKLB023 is a synthetic small-molecule compound which exerts potent anti-inflammatory effects in our previous studies. Here, this study aimed to characterize the protective effect of SKLB023 on SA-AKI and explore its underlying mechanism. The SA-AKI experimental models have been established by cecum ligation/puncture (CLP) and lipopolysaccharide (LPS) injection in male C57BL/6J mice. SKLB023 was administered by gavage (50 or 25 mg/kg in CLP model and 50 mg/kg in LPS model) daily 3 days in advance and 30 min earlier on the day of modeling. Our results confirmed SKLB023 treatment could improve the survival of SA-AKI mice and ameliorate renal pathological injury, inflammation, and apoptosis in the two types of septic AKI mice. Mechanically, SKLB023 deceased the expression of TLR4 in LPS-triggered renal tubular epithelial cells, and inhibited the activation of downstream pathways including NF-κB and MAPK pathways. Our study suggested that SKLB023 is expected to be a potential drug for the prevention and treatment of septic AKI.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Lipopolissacarídeos
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Apoptose
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Sepse
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Receptor 4 Toll-Like
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Injúria Renal Aguda
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Camundongos Endogâmicos C57BL
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Anti-Inflamatórios
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Int Immunopharmacol
Ano de publicação:
2024
Tipo de documento:
Article