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Updated: May 19, 2026
Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
Dapagliflozin attenuates cisplatin-induced nephrotoxicity in rats through modulation of ROS/NF-κB, BCL2/Bax and
Esraa K Khallaf1, Eman A Ramadan2, Mohey M Elmazar2
1Department of Pharmacology and Biochemistry, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt. Esraa.Khallaf@bue.edu.eg.
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.
Insights
Dapagliflozin protects against cisplatin nephrotoxicity by activating PINK1/Parkin-mediated mitophagy and reducing inflammation and apoptosis. This study highlights its potential renal protective effects beyond diabetes management.
Area of Science:
- Nephrology
- Pharmacology
- Molecular Biology
Background:
- Dapagliflozin (DPG) shows renal protective effects.
- Its impact on mitophagy in cisplatin (CIS)-induced nephrotoxicity is not well understood.
Purpose of the Study:
- To investigate DPG's protective effects against CIS nephrotoxicity in rats.
- To explore the role of PINK1/Parkin-mediated mitophagy, inflammation, and apoptosis.
Main Methods:
- Male Sprague Dawley rats received DPG (10 mg/kg) daily for 14 days.
- Acute kidney injury (AKI) was induced with CIS (7 mg/kg).
- Evaluated renal function, oxidative stress, inflammation, apoptosis, and mitophagy markers.
Main Results:
- DPG reduced kidney damage, lowering NGAL, KIM-1, MDA, and NO, while increasing GSH.
- DPG mitigated inflammatory (NF-κB, TNF-α, IL-6) and apoptotic (Bax, cleaved caspase-3) markers.
- DPG restored mitophagy by increasing PINK1, Parkin, and LC3II/LC3I, and decreasing TIMM23, TOMM20, and p62.
Conclusions:
- DPG prevents CIS nephrotoxicity.
- DPG likely acts by activating PINK1/Parkin-mediated mitophagy and reducing oxidative stress and apoptosis.
