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Baicalin Alleviates Contrast-Induced Acute Kidney Injury Through ROS/NLRP3/Caspase-1/GSDMD Pathway-Mediated Proptosis in vitro.

Authors
  • Li, Yanyan1, 2
  • Wang, Junda2
  • Huang, Dan2
  • Yu, Chao1
  • 1 College of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China. , (China)
  • 2 Chongqing Traditional Chinese Medicine Hospital, Chongqing, People's Republic of China. , (China)
Type
Published Article
Journal
Drug Design Development and Therapy
Publisher
Dove Medical Press
Publication Date
Jan 01, 2022
Volume
16
Pages
3353–3364
Identifiers
DOI: 10.2147/DDDT.S379629
PMID: 36196145
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

To investigate the effect of baicalin on the reactive oxygen species (ROS)/ NOD-like receptor protein 3 (NLRP3)/Caspase-1/gasdermin-D (GSDMD) inflammasome pathway and its related mechanism in regulating pyroptosis of human renal tubular epithelial cells (HK-2) induced by contrast media. Iohexol was used to act on HK-2 cells to establish a renal tubular cell pyroptosis model; and the signal pathway genes were silenced, cytokines were detected by enzyme-linked immunosorbent assay (ELISA), and cell viability, gene expression, and protein expression were evaluated by double fluorescence staining and flow cytometry. To assess the cytotoxicity caused by the contrast agent; cells were pretreated with different concentrations of baicalin; and then the cells were exposed to iohexol again, and the relevant indicators were tested again. After HK-2 cells were exposed to iohexol, the NLRP3 inflammasome pathway markers NLRP3, interleukin (IL)-1β, and IL-18 mRNA levels as well as the protein expression levels of NLRP3, ASC, Caspase-1, and GSDMD were up-regulated. In addition, the effect also significantly increased the IL-18, IL-1β, lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) release, and cellular ROS levels. The results of Annexin V-FITC/PI flow cytometry showed that the level of apoptosis was increased. However, after the intervention of baicalin, the changes in the above indexes caused by iohexol stimulation of HK-2 cells were inhibited. Exposure to iohexol can induce pyroptosis of HK-2 cells through the ROS/NLRP3/Caspase-1/GSDMD signaling pathway. Baicalin ameliorated iohexol-induced pyroptosis in HK-2 cells by regulating the NLRP3 inflammasome pathway. © 2022 Li et al.

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