Resveratrol attenuates tubular injury in diabetic kidney disease by suppressing the ferroptosis–ferritinophagy pathway
- 1Department of Nephrology, Affiliated Hospital of Panzhihua University, Panzhihua, Sichuan Province 617000 China
- 2Department of Nephrology, Chinese and Western Medicine Hospital of Panzhihua, Panzhihua, Sichuan Province 617000 China
- 3Department of Health Management Centre, Chongqing Academy of Medical Sciences, Chongqing General Hospital, Chongqing University, Chongqing, 401147 China
Abstract
Background: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, and renal oxidative stress (OS)–mediated tubular injury plays a critical role in its progression. Resveratrol (Res) possesses established antioxidative properties, yet its mechanistic involvement in ferroptosis-ferritinophagy signaling remains unclear. This study investigated the protective effects of Res on renal tubular injury in DKD and explored its regulatory role in the ferroptosis–ferritinophagy pathway.
Methods: A DKD mouse model was established using unilateral nephrectomy followed by streptozotocin injection. A total of 42 male C57BL/6 N mice were used in this study. Six mice served as the blank control group, and the remaining 36 underwent model induction. The 30 successfully modeled mice were randomly divided into 5 groups (n = 6 per group): the DKD group, the positive control group (perindopril 0.48 mg/kg/d), and the resveratrol (Res) low-, medium-, and high-dose groups (1.0, 2.5, 5.0 mg/kg/d, administered by gavage for 8 weeks). Renal function, oxidative stress markers, and renal tubular injury markers were assessed. Hematoxylin and eosin (H&E) staining, Masson staining, 4-hydroxynonenal (4-HNE) immunofluorescence, and Western blotting (for ferroptosis/ferritinophagy-related proteins) were performed.
Results: Compared with the Black group, DKD group mice exhibited marked OS, tubular injury, and activation of the ferroptosis–ferritinophagy axis. Res treatment significantly reduced fasting blood glucose, SCr, BUN, 24-hour urinary protein, MDA, Fe²⁺, β2-MG, RBP4, and NGAL levels, while elevating T-SOD and GSH-Px (P < 0.05). Res also downregulated Nrf2, SLC7A11, GPX4, LC3II/LC3I, and FTH1, alongside increased expression of p62 and NCOA4, demonstrating a clear dose-dependent effect.
Conclusion: Resveratrol markedly attenuates renal oxidative stress and tubular injury in DKD. These findings suggest that its renoprotective effects may be mediated through inhibition of the ferroptosis–ferritinophagy pathway, highlighting Res as a promising therapeutic candidate for DKD.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s41065-026-00718-2.
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BibTeX
@article{zhu2026resveratrol,
title = {{Resveratrol attenuates tubular injury in diabetic kidney disease by suppressing the ferroptosis–ferritinophagy pathway}},
author = {Dongju Zhu and Longhui Li},
journal = {Hereditas},
year = {2026},
month = aug,
doi = {10.1186/s41065-026-00718-2},
url = {https://doi.org/10.1186/s41065-026-00718-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Resveratrol attenuates tubular injury in diabetic kidney disease by suppressing the ferroptosis–ferritinophagy pathway
AU - Dongju Zhu
AU - Longhui Li
PY - 2026
DA - 2026/08/08
JO - Hereditas
DO - 10.1186/s41065-026-00718-2
UR - https://doi.org/10.1186/s41065-026-00718-2
AB - Background: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, and renal oxidative stress (OS)–mediated tubular injury plays a critical role in its progression. Resveratrol (Res) possesses established antioxidative properties, yet its mechanistic involvement in ferroptosis-ferritinophagy signaling remains unclear. This study investigated the protective effects of Res on renal tubular injury in DKD and explored its regulatory role in the ferroptosis–ferritinophagy pathway. Methods: A DKD mouse model was established using unilateral nephrectomy followed by streptozotocin injection. A total of 42 male C57BL/6 N mice were used in this study. Six mice served as the blank control group, and the remaining 36 underwent model induction. The 30 successfully modeled mice were randomly divided into 5 groups (n = 6 per group): the DKD group, the positive control group (perindopril 0.48 mg/kg/d), and the resveratrol (Res) low-, medium-, and high-dose groups (1.0, 2.5, 5.0 mg/kg/d, administered by gavage for 8 weeks). Renal function, oxidative stress markers, and renal tubular injury markers were assessed. Hematoxylin and eosin (H&E) staining, Masson staining, 4-hydroxynonenal (4-HNE) immunofluorescence, and Western blotting (for ferroptosis/ferritinophagy-related proteins) were performed. Results: Compared with the Black group, DKD group mice exhibited marked OS, tubular injury, and activation of the ferroptosis–ferritinophagy axis. Res treatment significantly reduced fasting blood glucose, SCr, BUN, 24-hour urinary protein, MDA, Fe²⁺, β2-MG, RBP4, and NGAL levels, while elevating T-SOD and GSH-Px (P < 0.05). Res also downregulated Nrf2, SLC7A11, GPX4, LC3II/LC3I, and FTH1, alongside increased expression of p62 and NCOA4, demonstrating a clear dose-dependent effect. Conclusion: Resveratrol markedly attenuates renal oxidative stress and tubular injury in DKD. These findings suggest that its renoprotective effects may be mediated through inhibition of the ferroptosis–ferritinophagy pathway, highlighting Res as a promising therapeutic candidate for DKD. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s41065-026-00718-2.
SN - 0018-0661
SN - 1601-5223
ER -