Entacapone alleviates acute kidney injury by inhibiting ferroptosis.

Abstract

Acute kidney injury (AKI) is a common clinical problem and an efficacious treatment is lacking. Ferroptosis, a newly discovered type of programmed cell death, has been reported to alleviate renal tubular injury in ischemia/reperfusion-induced acute kidney injury (I/R-AKI). Entacapone is a specific inhibitor of catechol-O-methyltransferase, which is used as an adjuvant drug against Parkinson's disease. We demonstrated that entacapone prevents renal I/R injury by inhibiting ferroptosis. Compared with a sham group, entacapone treatment mitigated I/R-induced pathological alterations, improved renal function, and inhibited ferroptosis. In HK-2 cells, entacapone treatment significantly reduced the lipid peroxidation and iron accumulation induced by the ferroptosis inducers erastin and RSL3, and significantly regulated expression of ferroptosis-related proteins. Entacapone upregulates p62 expression and affects the p62-KEAP1-NRF2 pathway, thereby upregulating nuclear translocation of NRF2. This action results in increased expression of the downstream SLC7A11, and significant suppression of oxidative stress and ferroptosis. Our results identify entacapone as a ferroptosis inhibitor that enhances antioxidant capacity. Entacapone may serve as a novel strategy to improve treatment of, and recovery from, I/R-AKI.

• Authors: Jiahong Yang, Xiaolin Sun, Ning Huang, Peng Li, Jiaqi He, Lan Jiang, Xuemei Zhang, Shu Han, Hong Xin
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 36 Issue 7 Pg. e22399 (07 2022) ISSN: 1530-6860 [Electronic] United States
• PMID: 35691001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Federation of American Societies for Experimental Biology.

Chemical References

• Catechols
• Kelch-Like ECH-Associated Protein 1
• NF-E2-Related Factor 2
• Nitriles
• entacapone
• Catechol O-Methyltransferase

Topics

• Acute Kidney Injury (metabolism)
• Catechol O-Methyltransferase (metabolism, therapeutic use)
• Catechols
• Ferroptosis
• Humans
• Kelch-Like ECH-Associated Protein 1 (metabolism)
• NF-E2-Related Factor 2 (metabolism)
• Nitriles
• Reperfusion Injury (drug therapy, metabolism)