Kidney Week

Abstract: TH-PO121

Imperatorin Ameliorates Ferroptosis-Associated Cell Death, Inflammation, and Kidney Fibrosis in a Unilateral Ureteral Obstruction Mouse Model

Session Information

• Pharmacology
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

• 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

• Wu, Cheng-Tien, China Medical University Hospital, Taichung, Taiwan

Cheng-Tien Wu, PhD

• Lin, Ssu-chia, China Medical University Hospital, Taichung, Taiwan

Ssu-chia Lin, MS

• Chen, Yu-Syuan, China Medical University Hospital, Taichung, Taiwan

Yu-Syuan Chen, MS

• Weng, Pei-Yu, China Medical University Hospital, Taichung, Taiwan

Pei-Yu Weng, MS

• Kuo, Huey-liang, China Medical University Hospital, Taichung, Taiwan

Huey-liang Kuo, MD

• Chiang, Chih-Kang, National Taiwan University, Taipei, Taiwan

Chih-Kang Chiang, MD, PhD

• Liu, Shing-Hwa, National Taiwan University, Taipei, Taiwan

Shing-Hwa Liu, PhD

Group or Team Name

• Dept of Nutrition CMU.

Background

Chronic kidney disease (CKD) poses a global health problem with high prevalence, morbidity and mortality rates, and various complications. Imperatorin is a naturally occurring furocoumarin derivative and is found in traditional Chinese medicine Angelica Dahurica with anticancer, antihypertensive, and antidiabetic properties.

Methods

In this study, we aim to investigate the protective effects of imperatorin treatment and the specific underlying mechanisms on progressive CKD in a unilateral ureteral obstruction (UUO) mouse model.

Results

We found that imperatorin treatment alleviated kidney histology alternations, collagen depositions, and the protein expression of the fibrotic and EMT-related markers (Fibronectin, α-smooth muscle actin, E−cadherin, and Tumor growth factor-β). Additionally, we found the inhibition of the inflammatory cells infiltration, and moderation of the overload oxidative stress protein markers (Catalase, superoxide dismutase 2/SOD-2, NADPH oxidase 4/NOX-4, and thioredoxin reductase 1/Trxr-1). More important, administration imperatorin mitigates the induced ferroptosis (Cystine transporter SLC7A11/xCT, TFR-1, and Glutathione peroxidase 4/GPX4) as well as renal cell apoptotic death.

Conclusion

Our results suggested that imperatorin treatment improves the fibrotic features of CKD, inflammatory cell infiltration, oxidative stress overload, and ferroptosis-related apoptosis in UUO mice, highlighting its potential as a therapeutic target for CKD treatment in the future.