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Abstract: SA-PO266

Dapagliflozin Ameliorates Cisplatin-Induced Nephrotoxicity by Upregulating Nuclear Factor Erythroid 2-Related Factor 2/Heme Oxygenase-1 Signaling Pathway: A Pre-Clinical Molecular Approach

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 2000 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Nair, Anuradha Asokan, Ras Al Khaimah Medical and Health Sciences University College of Medical Sciences, Ras Al Khaimah, Ra’s al Khaymah, United Arab Emirates
  • Farook, Mohamed, Ras Al Khaimah Medical and Health Sciences University College of Medical Sciences, Ras Al Khaimah, Ra’s al Khaymah, United Arab Emirates
  • Binu, Nirmal Nachiketh, Ras Al Khaimah Medical and Health Sciences University College of Medical Sciences, Ras Al Khaimah, Ra’s al Khaymah, United Arab Emirates
  • Khan, Sofiya, Ras Al Khaimah Medical and Health Sciences University College of Medical Sciences, Ras Al Khaimah, Ra’s al Khaymah, United Arab Emirates
  • Mohamed Mustafa, Mohamed Yehya, Ras Al Khaimah Medical and Health Sciences University College of Medical Sciences, Ras Al Khaimah, Ra’s al Khaymah, United Arab Emirates
  • Khan, Mohammed Moin, Ras Al Khaimah Medical and Health Sciences University College of Medical Sciences, Ras Al Khaimah, Ra’s al Khaymah, United Arab Emirates
  • Satyam, Shakta Mani, Ras Al Khaimah Medical and Health Sciences University College of Medical Sciences, Ras Al Khaimah, Ra’s al Khaymah, United Arab Emirates
  • Bairy, Laxminarayana Kurady, Ras Al Khaimah Medical and Health Sciences University College of Medical Sciences, Ras Al Khaimah, Ra’s al Khaymah, United Arab Emirates
  • Rehman, Abdul, Ras Al Khaimah Medical and Health Sciences University College of Medical Sciences, Ras Al Khaimah, Ra’s al Khaymah, United Arab Emirates

Group or Team Name

  • Dr. Satyam's Lab - DAPA CKD Team.
Background

A dose-limiting side effect of cisplatin administration is nephrotoxicity which impairs a patient's quality of life. No potent nephroprotective agent is available to combat cisplatin-induced nephrotoxicity. This study aimed to explore the nephroprotective potential of dapagliflozin and silymarin alone and in combination against cisplatin-induced nephrotoxicity in Wistar rats.

Methods

30 adult Wistar rats were randomly divided into five groups (n=6/group): Group I- Normal control, Group II- Negative control, Group- III- Silymarin, Group IV- Dapagliflozin and Group V- Dapagliflozin + Silymarin. Nephrotoxicity was induced in Group II to Group V by administering cisplatin weekly for seven weeks. Biomarkers for kidney injury, inflammation, and oxidative stress were estimated following a histopathological examination of the kidney.

Results

Chronic kidney disease was significantly (p<0.05) demonstrated in cisplatin-intoxicated (negative) control
compared to normal control rats. Dapagliflozin alone and in combination with silymarin significantly (p<0.05) reduced serum urea, creatinine, inflammatory cytokines, and oxidative stress markers compared to negative control.

Conclusion

The present study revealed that dapagliflozin alone and in combination with silymarin ameliorates cisplatin-induced nephrotoxicity in Wistar rats via stimulating Nrf2/HO-1 signaling pathway.