Fluorofenidone Attenuates Renal Interstitial Fibrosis by Enhancing Autophagy and Retaining Mitochondrial Function.
Cell Biochem Biophys
; 81(4): 777-785, 2023 Dec.
Article
en En
| MEDLINE
| ID: mdl-37735328
ABSTRACT
BACKGROUND:
Fluorofenidone (AKF-PD) is a novel pyridone agent and has potent anti-NLRP3 inflammasome and anti-fibrotic activities. However, the mechanisms underlying its pharmacological actions are not fully understood.METHODS:
A renal fibrosis rat model was established by the unilateral ureteral obstruction (UUO) procedure and the rats were randomized and treated with, or without, AKF-PD for 3 and 7 days. The levels of renal fibrosis, NLRP3 inflammasome activation, mitochondrial function, and autophagy were tested in rat kidney tissues. Macrophages following lipopolysaccharides (LPS) and adenosine 5'-triphosphate (ATP) stimulation were examined by Western blot, spectrophotometry, and TEM.RESULTS:
Compared with the untreated UUO rats, AKF-PD treatment significantly mitigated the UUO procedure-induced renal fibrosis in rats. AKF-PD treatment decreased mitochondrial dysfunction and IL-Iß and caspase-1 expression in rat kidney tissues and reduced mitochondrial reactive oxygen species production in activated macrophages. Mechanistically, AKF-PD treatment significantly attenuated the PI3K/AKT/mTOR signaling, increased Beclin-1 and LC3 II expression and autophagosome formation, and ameliorated the mitochondrial damage in renal tissues and activated macrophages.CONCLUSION:
The results indicated that AKF-PD treatment inhibited renal interstitial fibrosis by regulating the autophagy-mitochondria-NLRP3 inflammasome pathway.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Obstrucción Ureteral
/
Enfermedades Renales
Tipo de estudio:
Clinical_trials
Límite:
Animals
Idioma:
En
Revista:
Cell Biochem Biophys
Asunto de la revista:
BIOFISICA
/
BIOQUIMICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China