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Small-Dose Sunitinib Modulates p53, Bcl-2, STAT3, and ERK1/2 Pathways and Protects against Adenine-Induced

Mohamed A Saleh1,2, Ahmed M Awad2, Tarek M Ibrahim2

  • 1Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, UAE.

Pharmaceuticals (Basel, Switzerland)
|November 20, 2020
PubMed

Insights

Sunitinib protects against kidney injury by blocking tyrosine kinase signaling, reducing fibrosis, and enhancing antioxidant defenses. This study demonstrates sunitinib

Area of Science:

  • Nephrology
  • Pharmacology
  • Molecular Biology

Background:

  • Nephrotoxicity from medications limits therapeutic options.
  • Tyrosine kinase signaling pathways are implicated in kidney injury.

Purpose of the Study:

  • To investigate if blocking tyrosine kinase signaling with sunitinib protects against adenine-induced nephrotoxicity.
  • To evaluate sunitinib's effects on kidney function, oxidative stress, and specific molecular markers.

Main Methods:

  • Adult male Swiss albino mice were divided into four groups: control, adenine-induced nephrotoxicity, sunitinib treatment, and combined adenine+sunitinib treatment.
  • Kidney function, oxidative stress biomarkers, tubular injury, and histopathological changes were assessed.
  • Renal expression of key proteins including Bcl-2, p53, TGF-β1, p-ERK1/2, and phospho-STAT3 was measured.

Main Results:

  • Sunitinib significantly improved kidney function and antioxidant biomarkers in mice with adenine-induced nephrotoxicity.
  • The sunitinib group showed reduced kidney fibrosis, tubular injury, and increased p53 expression.
  • Sunitinib decreased TGF-β1, p-ERK1/2, and phospho-STAT3 levels while increasing Bcl-2 expression.

Conclusions:

  • Sunitinib effectively mitigates chemically induced nephrotoxicity by targeting profibrogenic pathways.
  • The drug demonstrates anti-apoptotic effects and antioxidant capabilities, offering potential therapeutic benefits.
  • Blocking VEGFR and PDGFR signaling with sunitinib presents a promising strategy for preventing kidney injury.
Keywords:
Bcl-2ERK1/2TGF-β1nephrotoxicityp53sunitinib

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