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Dasatinib and Quercetin Combination Increased Kidney Damage in Acute Folic Acid-Induced Experimental Nephropathy

Antonio Battaglia-Vieni1,2, Vanessa Marchant1,2, Lucia Tejedor-Santamaria1,2

  • 1Molecular and Cellular Biology in Renal and Vascular Pathology Laboratory, Department of Medicine, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Avda. Reyes Católicos, 2, 28040 Madrid, Spain.

Pharmaceuticals (Basel, Switzerland)
|June 27, 2025
PubMed

Insights

The senolytic drug combination of dasatinib plus quercetin (D&Q) did not protect against acute kidney injury (AKI) in mice. D&Q treatment exacerbated some harmful responses, suggesting caution for clinical translation in AKI.

Area of Science:

  • Nephrology
  • Gerontology
  • Cellular Biology

Background:

  • Acute kidney injury (AKI) is a significant clinical challenge with high mortality and progression to chronic kidney disease (CKD), particularly in the elderly.
  • Cellular senescence is implicated in AKI, CKD, and aging, presenting a potential therapeutic target.
  • Senolytics, such as dasatinib plus quercetin (D&Q), show promise in conditions like experimental CKD, but their efficacy in AKI is unknown.

Purpose of the Study:

  • To investigate the therapeutic potential of the senolytic drug combination dasatinib plus quercetin (D&Q) in a murine model of acute kidney injury.
  • To evaluate the effects of D&Q on renal function, kidney damage biomarkers, cellular senescence markers, and antiaging factors in the context of AKI.

Main Methods:

  • A folic acid-induced nephrotoxicity (FAN-AKI) mouse model was utilized to study AKI.
  • Mice were pretreated with the D&Q combination before induction of AKI.
  • Renal function (serum creatinine, BUN), gene expression of kidney damage and senescence markers, p21-positive senescent cells, and Klotho levels were assessed.

Main Results:

  • D&Q pretreatment failed to prevent renal dysfunction in the acute phase of FAN-AKI, as indicated by serum creatinine and BUN levels.
  • D&Q treatment significantly increased the expression of kidney damage biomarkers (Lcn2, Havcr1), p21, and senescence-associated secretory phenotype genes.
  • The number of senescent p21-positive cells and the downregulation of Klotho remained unchanged by D&Q treatment in injured kidneys.

Conclusions:

  • The senolytic drug combination D&Q demonstrated no protective effect in folic acid-induced acute kidney injury.
  • D&Q treatment exacerbated certain detrimental responses in the FAN-AKI model, highlighting potential risks.
  • These findings suggest caution is warranted regarding the clinical translation of D&Q for AKI treatment.
Keywords:
Klothoacute kidney injurydasatinibp21quercetinsenescencesenolytics

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