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Updated: Aug 22, 2025
Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice
Published on: August 9, 2013
Empagliflozin protects against renal ischemia/reperfusion injury in mice
Qifeng Wang1, Feng Ju1, Jiaxue Li1
1Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Abstract:
Renal ischemia/reperfusion (I/R) can induce acute kidney injury. Empagliflozin is a newly developed inhibitor of sodium-glucose cotransporter-2 (SGLT2) approved as an antidiabetic medication for patients with type 2 diabetes mellitus. Despite the established cardioprotective functions of empagliflozin, its protective role in renal I/R is unclear. Here, the present study evaluated the renoprotective effects of empagliflozin in a mouse model of renal I/R injury. Male C57/BL6 mice were allocated to sham-operated, I/R, and empagliflozin groups. Kidney pedicles on both sides were clamped for 45 min and were reperfused for 24 h. Empagliflozin (1 mg/kg) was administered to the mice for 2 days preischemia. The GSK-3β inhibitor SB216763 was administered intravenously at the beginning of reperfusion (0.1 mg/kg). Renal function and histological scores were evaluated. The kidneys were taken for immunohistochemical analysis, western blotting and apoptosis measurements. We found that empagliflozin decreased serum levels of creatinine and urea, reduced the average kidney weight-to-tibia length ratio, attenuated tubular damage, reduced renal proinflammatory cytokine expression and inhibited apoptosis in injured kidneys. Furthermore, empagliflozin increased renal glycogen synthase kinase 3β (GSK-3β) phosphorylation post I/R. Pharmacological inhibition of GSK-3β activity mimicked the renal protective effects offered by empagliflozin. In summary, these results support a protective role of empagliflozin against renal I/R injury.
Insights
Empagliflozin, an SGLT2 inhibitor, protects against kidney injury from renal ischemia/reperfusion (I/R). It reduces damage and inflammation by modulating GSK-3β activity, offering potential therapeutic benefits for acute kidney injury.
Area of Science:
- Nephrology
- Pharmacology
- Molecular Biology
Background:
- Renal ischemia/reperfusion (I/R) injury is a significant cause of acute kidney injury.
- Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, has known cardioprotective effects, but its role in renal I/R is not well-defined.
Purpose of the Study:
- To investigate the renoprotective effects of empagliflozin in a mouse model of renal I/R injury.
- To explore the underlying molecular mechanisms, particularly the involvement of glycogen synthase kinase 3β (GSK-3β).
Main Methods:
- Male C57/BL6 mice underwent renal I/R injury with sham-operated controls.
- Empagliflozin was administered pre-ischemia; a GSK-3β inhibitor (SB216763) was given at reperfusion.
- Evaluated renal function (creatinine, urea), histology, inflammation, apoptosis, and GSK-3β phosphorylation.
Main Results:
- Empagliflozin treatment significantly reduced serum creatinine and urea levels.
- It attenuated tubular damage, decreased proinflammatory cytokines, and inhibited apoptosis in injured kidneys.
- Empagliflozin increased GSK-3β phosphorylation, and GSK-3β inhibition mimicked its protective effects.
Conclusions:
- Empagliflozin demonstrates significant renoprotective effects against I/R-induced acute kidney injury in mice.
- These benefits are associated with the modulation of GSK-3β signaling pathways.
- Empagliflozin represents a potential therapeutic strategy for preventing or treating renal I/R injury.
