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Published on: May 10, 2024
Notch inhibitor mitigates renal ischemia‑reperfusion injury in diabetic rats
1Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Abstract:
Diabetes mellitus can exacerbate renal ischemia‑reperfusion (I/R) injury (RI/RI) in diabetic rats. Previous studies have shown that Notch signaling is involved in renal disorders. The aim of the present study was to evaluate the protective effect of the Notch inhibitor γ‑secretase N‑[N‑(3,5‑difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butyl ester (DAPT) on RI/RI in a streptozocin (STZ)‑induced diabetic rat model. STZ‑induced diabetic rats were randomly grouped for different treatments. Cisplatin was used to trigger the Notch signaling pathway and the animals were preconditioned with DAPT to block the signaling pathway. Renal function, oxidative stress and inflammatory factors were examined. DAPT‑treated diabetic rats demonstrated mitigated renal injury and function, antioxidative activity was significantly improved and HIF‑1a was upregulated. Notch inhibitor DAPT is a potential therapeutic target to improve the outcome of RI/RI in STZ‑induced diabetic rats in part via the regulation of anti‑oxidation and HIF‑1a.
Insights
The Notch inhibitor DAPT mitigates renal ischemia-reperfusion injury in diabetic rats by improving kidney function and enhancing antioxidative activity. This suggests DAPT as a potential therapy for diabetic kidney injury.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Diabetes mellitus exacerbates renal ischemia-reperfusion (I/R) injury.
- Notch signaling pathway is implicated in renal disorders.
Purpose of the Study:
- To evaluate the protective effect of the Notch inhibitor DAPT on renal I/R injury in a streptozocin-induced diabetic rat model.
- To investigate the underlying mechanisms involving anti-oxidation and HIF-1a.
Main Methods:
- Streptozocin-induced diabetic rats were used and divided into treatment groups.
- Renal I/R injury was induced, and animals were preconditioned with DAPT to inhibit Notch signaling.
- Renal function, oxidative stress markers, inflammatory factors, and HIF-1a expression were assessed.
Main Results:
- DAPT treatment significantly mitigated renal injury and improved renal function in diabetic rats.
- Antioxidative activity was markedly enhanced, and HIF-1a was upregulated in DAPT-treated rats.
- These findings suggest a protective role of DAPT against renal I/R injury in diabetes.
Conclusions:
- The Notch inhibitor DAPT demonstrates a therapeutic potential for improving outcomes of renal I/R injury in diabetic rats.
- DAPT's protective effects are partly mediated through the regulation of anti-oxidation and HIF-1a.
- DAPT represents a promising therapeutic target for managing diabetic kidney injury.
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