Dapagliflozin prevented cisplatin-induced nephrotoxicity in rats by activating PINK1/Parkin-mediated mitophagy and attenuating oxidative stress and apoptotic activity.
Does dapagliflozin prevent cisplatin-induced nephrotoxicity in rats?
Dapagliflozin prevents cisplatin-induced nephrotoxicity in a rat model by activating PINK1/Parkin-mediated mitophagy and attenuating oxidative stress and apoptosis.
Abstract 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.
Khallaf et al. (2026) studied Cisplatin-induced nephrotoxicity. Dapagliflozin vs. Cisplatin alone was evaluated on Glomerular and tubular damage, oxidative stress, inflammatory, apoptotic, and mitophagy markers. Dapagliflozin prevented cisplatin-induced nephrotoxicity in rats by activating PINK1/Parkin-mediated mitophagy and attenuating oxidative stress and apoptotic activity.