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

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.

• Authors: Yi-Wei Du, Xiao-Kang Li, Ting-Ting Wang, Lu Zhou, Hui-Rong Li, Lan Feng, Heng Ma, Hong-Bao Liu
• Journal: Molecular medicine (Cambridge, Mass.) (Mol Med) Vol. 29 Issue 1 Pg. 42 (04 03 2023) ISSN: 1528-3658 [Electronic] England
• PMID: 37013504 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• cyanidin-3-O-beta-glucopyranoside
• AMP-Activated Protein Kinases
• Reactive Oxygen Species
• Iron
• Lipids

Topics

• Animals
• Mice
• AMP-Activated Protein Kinases
• Ferroptosis
• Reactive Oxygen Species
• Acute Kidney Injury (drug therapy, etiology)
• Reperfusion Injury (drug therapy)
• Iron
• Ischemia
• Lipids