4.5 Article

Curcumin attenuates renal interstitial fibrosis by regulating autophagy and retaining mitochondrial function in unilateral ureteral obstruction rats

期刊

BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
卷 128, 期 4, 页码 594-604

出版社

WILEY
DOI: 10.1111/bcpt.13550

关键词

autophagy; curcumin; mitochondria; renal interstitial fibrosis; unilateral ureteral obstruction

资金

  1. National Natural Science Foundation of China [81700625]
  2. Doctoral Start-up Foundation of Liaoning Province [20170520273]
  3. Department of Education of Liaoning Province [JYTJCZR2020060, JYTQN2020041]

向作者/读者索取更多资源

Curcumin has shown promising effects in attenuating renal interstitial fibrosis in UUO rats by inhibiting NLRP3 inflammasome activation, improving mitochondrial function, and promoting autophagy. Its mechanism of action also involves inhibiting the PI3K/AKT/mTOR pathway.
Renal interstitial fibrosis (RIF) is the leading cause of end-stage renal disease, partly because of the lack of effective treatments. Curcumin, the primary active ingredient in turmeric, reportedly exerts potent antifibrotic effects. This study investigated the effects of curcumin on RIF in unilateral ureteral obstruction (UUO) rats and characterized the underlying action mechanism. UUO rats were treated with curcumin for 7 and 14 d. Renal fibrosis was evaluated through haematoxylin-eosin staining, Masson staining, and type I and III collagen expression. Autophagy and mitochondria were observed through scanning electron microscopy. NLRP3 inflammasomes, mitochondria, and autophagy-related proteins were detected through Western blotting. Mitochondrial respiratory enzyme activity was assessed spectrophotometrically. Compared with UUO rats, renal fibrosis was attenuated and NLRP3 inflammasome activation was inhibited in curcumin-treated rats. Furthermore, mitochondrial dysfunction was ameliorated and the LC3B/LC3A ratio and Beclin-1 expression were increased in curcumin-treated rats. Additionally, curcumin inhibited the PI3K/AKT/mTOR pathway. These results indicate that curcumin is a promising treatment agent for RIF, and its antifibrotic effects may be mediated by the inhibition of NLRP3 inflammasome activity through the regulation of autophagy and protection of mitochondrial function in UUO rats.

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