Dapagliflozin attenuates ferroptosis in diabetic nephropathy through activation of the Nrf2/HO‑1 signaling pathway
Year: 2026
Type: article
Abstract: Renal tubular injury has emerged as a critical determinant in the pathogenesis of diabetic nephropathy (DN). Ferroptosis, a recently characterized mode of iron‑dependent regulated cell death, has been implicated in the development of renal tubular damage. Dapagliflozin (DAPA), a sodium‑glucose cotransporter 2 inhibitor, has demonstrated efficacy in attenuating DN progression and preserving renal function. The present study sought to elucidate the inhibitory mechanisms by which DAPA modulates ferroptosis in DN. To this aim, the expression profiles of key molecular markers within the ferroptosis cascade were systematically evaluated using 6‑week‑old male C57BL/6J mice and high‑glucose‑cultured human renal tubular epithelial cells as experimental models. The findings revealed that DAPA notably ameliorated renal histopathological alterations, upregulated the expression of solute carrier family 7 member 11, glutathione peroxidase 4 and ferritin heavy chain 1, whilst concomitantly downregulating transferrin receptor 1. These effects were mediated through the activation of nuclear factor erythroid 2‑related factor 2 (Nrf2) and heme oxygenase‑1 (HO‑1) in C57BL/6J mice. Collectively, these data indicate that the reno‑protective effects of DAPA in DN may be attributable to the suppression of ferroptosis via activation of the Nrf2/HO‑1 signaling axis.
Authors: Hanshuang Liu, Xiaoxiao Zhang, Yubing Cui, Shengxi Xiong, Linjuan Huang, Min Li, Chen Shao, Xiaolei Hu
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7160204170