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

Battaglia-Vieni, Antonio, Marchant, Vanessa, Tejedor-Santamaria, Lucia, García-Caballero, Cristina, Flores-Salguero, Elena, Ruiz-Torres, María Piedad, Rayego-Mateos, Sandra, Sanz, Ana Belen, Ortiz, Alberto, Ruiz-Ortega, Marta·2025·Pharmaceuticals
DOI 10.3390/ph18060822PMC PMC12195755
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Abstract

Background/Objectives: Acute kidney injury (AKI) remains an unsolved medical problem due to the lack of effective treatments, high mortality, and increased susceptibility to progression to chronic kidney disease (CKD), especially in the elderly. Cellular senescence has been described in AKI, CKD, and aging and has been proposed as a promising therapeutic target. The senolytic drug combination of dasatinib plus quercetin (D&Q) is beneficial in some pathological conditions, including experimental CKD, but there are no data for AKI. Methods: The effect of D&Q combination was tested in folic acid-induced nephrotoxicity (FAN-AKI), a murine AKI model. Results: D&Q pretreatment did not prevent renal dysfunction in the acute phase of FAN-AKI, as determined by serum creatinine and BUN levels at 48 h. Moreover, gene expression of the kidney damage biomarkers Lcn2 and Havcr1, the Cdkn1a gene, which encodes p21, and some genes encoding components of the senescent cell secretome were significantly increased in response to D&Q treatment. The number of senescent p21-positive cells in injured kidneys was similar in untreated or D&Q-treated FAN mice. In addition, D&Q did not prevent the downregulation of the antiaging factor Klotho in damaged kidneys. Conclusions: D&Q treatment was not protective in FAN-AKI, exacerbating some deleterious responses. These results suggest caution when exploring the clinical translation of D&Q senolytic activity.

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Metadata

Authors
Battaglia-Vieni, A., Marchant, V., Tejedor-Santamaria, L., García-Caballero, C., Flores-Salguero, E., Ruiz-Torres, M. P., Rayego-Mateos, S., Sanz, A. B., Ortiz, A., & Ruiz-Ortega, M.
Venue
Pharmaceuticals
Publisher
MDPI AG
Published
2025-05-30
Volume
18
Issue
6
Pages
822
ISSN
1424-8247
DOI
10.3390/ph18060822
PMC
PMC12195755
Cited by
6
References
14
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • European Union (RICORS2040-RENAL, RD21/0005/0002, RD21/0005/0005, RD24/0004/0001, RD24/0004/0021, RD24/0004/0028, RD24/0004/0020, PI23/00394, PI24/00007, PI22/00469, Miguel Servet CP23/00025, PIPF-2023/SAL-GL-29648, P2022/BMD-7221)
  • Instituto de Salud Carlos III (ISCIII) (RICORS2040-RENAL, RD21/0005/0002, RD21/0005/0005, RD24/0004/0001, RD24/0004/0021, RD24/0004/0028, RD24/0004/0020, PI23/00394, PI24/00007, PI22/00469, Miguel Servet CP23/00025, PIPF-2023/SAL-GL-29648, P2022/BMD-7221)
  • Comunidad de Madrid (RICORS2040-RENAL, RD21/0005/0002, RD21/0005/0005, RD24/0004/0001, RD24/0004/0021, RD24/0004/0028, RD24/0004/0020, PI23/00394, PI24/00007, PI22/00469, Miguel Servet CP23/00025, PIPF-2023/SAL-GL-29648, P2022/BMD-7221)
  • INNOREN (RICORS2040-RENAL, RD21/0005/0002, RD21/0005/0005, RD24/0004/0001, RD24/0004/0021, RD24/0004/0028, RD24/0004/0020, PI23/00394, PI24/00007, PI22/00469, Miguel Servet CP23/00025, PIPF-2023/SAL-GL-29648, P2022/BMD-7221)

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