Notch inhibitor mitigates renal ischemiareperfusion injury in diabetic rats

Xiaokai Duan1, Guijun Qin1

  • 1Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

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.