Scientific reportsMay 17, 2026

Dapagliflozin reduces kidney damage from cisplatin in rats by affecting cell stress and survival signals

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated May 19, 2026

Abstract

Dapagliflozin (DPG) significantly reduced renal damage in rats subjected to cisplatin-induced nephrotoxicity.

DPG administration lowered levels of injury markers such as NGAL and KIM-1.
Treatment with DPG decreased oxidative stress indicators, including malondialdehyde (MDA) and nitric oxide (NO), while increasing glutathione (GSH) levels.
DPG inhibited the expression of pro-inflammatory and apoptotic factors, such as NF-κB, TNF-α, IL-6, and Bax, while promoting BCL2 expression.
Caspase-3 activity, associated with apoptosis, was reduced in the presence of DPG.
DPG enhanced mitophagy, indicated by increased levels of PINK1, Parkin, and the LC3II/LC3I ratio, and decreased TIMM23, TOMM20, and p62 levels.

Simplified

Dapagliflozin (DPG), an anti-diabetic drug, has gained attention for its renal protective effects through multiple molecular pathways, yet its impact on mitophagy in cisplatin (CIS) nephrotoxicity remains unclear. This study aimed to examine the impact of DPG against CIS-induced nephrotoxicity in rats, targeting mainly PINK1/Parkin-mediated mitophagy and inflammatory/apoptotic pathways. Male Sprague Dawley rats received DPG (10 mg/kg; p.o) daily for 14 consecutive days and AKI was induced by a single injection of CIS (7 mg/kg; i.p) on day 10. Blood glucose, serum levels of creatinine and urea nitrogen, oxidative stress, inflammatory, apoptotic, mitophagy markers, and histological changes were assessed. DPG reduced glomerular and tubular damage by alleviating NGAL and KIM-1 protein expression as well as MDA and NO accompanied by enhanced GSH expression. It mitigated gene expression of NF-κB, TNF-α and IL-6 along with downregulation of Bax and upregulation of BCL2 mRNA expression. DPG prevented apoptotic activity through reduction in cleaved caspase-3 immunoreactivity. Moreover, DPG restored CIS-mediated mitophagy inhibition evidenced by elevation of PINK1, Parkin and LC3II/LC3I ratio and reduction of TIMM23, TOMM20 and p62. In conclusion, DPG prevents CIS nephrotoxicity probably, via activating PINK1/Parkin, meanwhile attenuating oxidative stress and apoptotic activity.

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Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The animal experiments were certified by the Ethics Committee of the British University in Egypt (EX-2318), in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

PubMed

Dapagliflozin reduces kidney damage from cisplatin in rats by affecting cell stress and survival signals

Abstract

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