Cyanidin-3-glucoside inhibits ferroptosis in renal tubular cells after ischemia/reperfusion injury via the AMPK pathway

Bibliographic Details
Title: Cyanidin-3-glucoside inhibits ferroptosis in renal tubular cells after ischemia/reperfusion injury via the AMPK pathway
Authors: Yi-Wei Du, Xiao-Kang Li, Ting-Ting Wang, Lu Zhou, Hui-Rong Li, Lan Feng, Heng Ma, Hong-Bao Liu
Source: Molecular Medicine, Vol 29, Iss 1, Pp 1-16 (2023)
Publisher Information: BMC, 2023.
Publication Year: 2023
Collection: LCC:Therapeutics. Pharmacology
LCC:Biochemistry
Subject Terms: Acute kidney injury (AKI), AMP-activated protein kinase (AMPK), Cyanidin-3-glucoside (C3G), Ferroptosis, Ischemia, Lipid peroxidation, Therapeutics. Pharmacology, RM1-950, Biochemistry, QD415-436
More Details: Abstract Background Ferroptosis, which is characterized by lipid peroxidation and iron accumulation, is closely associated with the pathogenesis of acute renal injury (AKI). Cyanidin-3-glucoside (C3G), a typical flavonoid that has anti-inflammatory and antioxidant effects on ischemia‒reperfusion (I/R) injury, can induce AMP-activated protein kinase (AMPK) activation. This study aimed to show that C3G exerts nephroprotective effects against I/R-AKI related ferroptosis by regulating the AMPK pathway. Methods Hypoxia/reoxygenation (H/R)-induced HK-2 cells and I/R-AKI mice were treated with C3G with or without inhibiting AMPK. The level of intracellular free iron, the expression of the ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4), and the levels of the lipid peroxidation markers 4-hydroxynonenal (4-HNE), lipid reactive oxygen species (ROS) and malondialdehyde (MDA) were examined. Results We observed the inhibitory effect of C3G on ferroptosis in vitro and in vivo, which was characterized by the reversion of excessive intracellular free iron accumulation, a decrease in 4-HNE, lipid ROS, MDA levels and ACSL4 expression, and an increase in GPX4 expression and glutathione (GSH) levels. Notably, the inhibition of AMPK by CC significantly abrogated the nephroprotective effect of C3G on I/R-AKI models in vivo and in vitro. Conclusion Our results provide new insight into the nephroprotective effect of C3G on acute I/R-AKI by inhibiting ferroptosis by activating the AMPK pathway.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1528-3658
Relation: https://doaj.org/toc/1528-3658
DOI: 10.1186/s10020-023-00642-5
Access URL: https://doaj.org/article/01647ab22cfe4ba295c5fc859dec1e2f
Accession Number: edsdoj.01647ab22cfe4ba295c5fc859dec1e2f
Database: Directory of Open Access Journals
More Details
ISSN:15283658
DOI:10.1186/s10020-023-00642-5
Published in:Molecular Medicine
Language:English