Dapagliflozin inhibits ferroptosis and ameliorates renal fibrosis in diabetic C57BL/6J mice.

IF 3.8 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Scientific Reports Pub Date : 2025-02-28 DOI:10.1038/s41598-025-91278-4

Zhen Zhang, Luxin Li, Yucen Dai, Yifei Lian, Haixu Song, Xin Dai, Ranyu Su, Jiaxing Yin, Ruimin Gu

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Abstract

Diabetic nephropathy (DN) is a common complication of diabetes and a major cause of end-stage renal disease, with complex pathogenesis involving inflammation, oxidative stress, fibrosis, and ferroptosis. Ferroptosis is linked to DN progression, yet treatment options are limited, particularly for targeting ferroptosis. Dapagliflozin (DAPA), an SGLT2 inhibitor, shows renal protective effects in diabetes, but its role in renal fibrosis and ferroptosis in DN is unclear. This study investigated DAPA's effect on renal fibrosis in DN by inhibiting ferroptosis, using a streptozotocin-induced diabetic mouse model. Results indicated that DAPA improved renal function, reduced fibrosis, and suppressed ferroptosis markers in diabetic mice. In vitro, DAPA inhibited ferroptosis and fibrosis in HK-2 cells under high glucose conditions. Molecular docking and network pharmacology suggested DAPA's anti-fibrotic and anti-ferroptotic effects may involve the Nrf2 and TGF-β signaling pathways. DAPA also reduced serum creatinine and blood urea nitrogen in diabetic mice, improved glomerulosclerosis and interstitial fibrosis, decreased iron deposition, and enhanced antioxidant activity. Overall, DAPA's multi-target mechanisms significantly improve DN progression, suggesting its potential as a targeted therapy against ferroptosis. Future studies should further explore DAPA's applications.

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来源期刊

Scientific Reports Natural Science Disciplines-

CiteScore

7.50

自引率

4.30%

发文量

19567

审稿时长

3.9 months

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