Cited by 35Chronic Kidney Disease and DiabetesRenal Diseases and GlomerulopathiesAcute Kidney Injury Research

Tirzepatide alleviates oxidative stress and inflammation in diabetic nephropathy via IL-17 signaling pathway

Yang, Yong, Wang, Yiyong, Zhou, Yong, Deng, Jing, Wu, Lihao·2025·Molecular and Cellular Biochemistry

Abstract

Oxidative stress (OS) and inflammation play essential roles in the development of diabetic nephropathy (DN). Tirzepatide (TZP) has a protective effect in diabetes. However, its underlying mechanism in DN remains unclear. DN model mice were induced by intraperitoneal injection of streptozotocin (STZ; 60 mg/kg), followed by administration of different doses of TZP (3 and 10 nmol/kg) via intraperitoneal injection for 8 weeks. The effects of TZP on DN were evaluated by detecting DN-related biochemical indicators, kidney histopathology, apoptosis, OS, and inflammation levels. Additionally, to further reveal the potential mechanism, we investigated the role of TZP in modulating the IL-17 pathway. TZP reduced serum creatinine (sCR), blood urea nitrogen (BUN), and advanced glycosylation end products (AGEs) levels, while simultaneously promoting insulin secretion in diabetic mice. Additionally, TZP attenuated tubular and glomerular injury and reduced renal apoptosis levels. Further studies found that TZP increased the levels of SOD and CAT, and decreased MDA. Meanwhile, TZP also reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in both mouse serum and kidney homogenates. TZP effectively inhibited the IL-17 pathway, and subsequent intervention with an IL-17 pathway agonist (IL-17A) reversed the suppressive effects of TZP on OS and inflammation. TZP can improve DN by inhibiting OS and inflammation through the suppression of the IL-17 pathway.

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Crossref · 10.1007/s11010-024-05066-1

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Authors
Yang, Y., Wang, Y., Zhou, Y., Deng, J., & Wu, L.
Affiliations
  • University of Hong Kong - Shenzhen Hospital (CN)
  • Ningxia Medical University (CN)
  • Southern Medical University Shenzhen Hospital (CN)
Corresponding author
Yang, Yong
Venue
Molecular and Cellular Biochemistry
Published
2024-07-04
Volume
480
Issue
2
Pages
1241-1254
ISSN
  • 0300-8177 (ISSN-L)
  • 1573-4919
OpenAlex
W4400312575
Cited by
35
References
51
Citations by year
2026: 12 · 2025: 21 · 2024: 2
FWCI
9.91
Type
journal article
Language
en
Open access
closed
Locations
  • Molecular and Cellular Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
Keywords
tirzepatide, diabetic nephropathy, oxidative stress, inflammation, IL-17 signaling, streptozotocin-induced diabetes, renal apoptosis, inflammatory cytokines, advanced glycation end products, insulin secretion, MDA
MeSH terms
Tirzepatide, Animals, Diabetes Mellitus, Experimental, Diabetic Nephropathies, Inflammation, Male, Signal Transduction, Oxidative Stress, Interleukin-17, Mice

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