Nephroprotective Role of Combined Sitagliptin and Oleuropein in Cisplatin-Induced Acute Kidney Injury: Regulation of SDF-1α/Nrf2/ HO-1 Axis and Autophagy | ||||
| Archives of Pharmaceutical Sciences Ain Shams University | ||||
| Article 12, Volume 5, Issue 2, December 2021, Page 354-370 PDF (1.64 MB) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/aps.2021.104714.1072 | ||||
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| Authors | ||||
Mohamed Bassiony1; Nesreen O Omar1; Amira M Badr2, 3; Nadia M Hamdy 4; Eman F Sanad  4
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| 1Department of Biochemistry, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt | ||||
| 2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt | ||||
| 3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia. | ||||
| 4Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt | ||||
| Abstract | ||||
| Background: Accumulating evidence proves that cisplatin, a widely used anticancer, causes acute kidney injury (AKI). Sitagliptin (Sita), a dipeptidyl peptidase-4 (DPP4) inhibitor, is a hypoglycemic agent that can promote tissue angiogenesis and cell survival. However, little is known about the nephroprotective effect of Sita in cisplatin-induced AKI especially its effect on SDF-1α, usually degraded by DPP4. Meanwhile, the olive oil component oleuropein (Ole) activates Nrf2/heme oxygenase-1 (HO-1) axis, which ultimately leads to SDF-1α activation. Herein, we studied the nephroprotective effects of combined Sita and Ole on oxidative stress and autophagy through SDF-1α/Nrf2/ HO-1 axis in cisplatin-induced AKI in rats. Methods: AKI was induced in vivo through single IP injection of cisplatin (7 mg/kg), while Sita (10 mg/kg) and Ole (16 mg/kg) were given separately and in combination for 7 days prior and 5 days after cisplatin injection. AKI was assessed through histopathological examination, measurement of serum creatinine and urea. Also, serum GLP-1, serum and kidney SDF-1α levels were measured by ELISA. LC3-II, P62, HO-1, Nrf2, and caspase-3 were investigated by western blotting. Results: Sita and Ole monotherapy and in combination accelerated kidney recovery as they suppress serum SDF-1α, serum BUN, creatinine and renal histopathological features. Each of Sita and Ole enhanced Nrf2/HO-1axis in renal tissues while only Sita enhanced renal SDF-1α. Sita and Ole monotherapy showed incompetent autophagy where the late steps of autophagy were incomplete. Combined treatment enhanced SDF-1α in kidney tissue which showed recovery through autophagy process. Conclusion: Sita and Ole show promising nephroprotective effects in cisplatin-induced AKI | ||||
| Keywords | ||||
| Cisplatin; Acute Kidney Injury; Sitagliptin; Oleuropein; SDF-1α; Nrf2; Autophagy; caspase-3 | ||||
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