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Original Research

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Protective effect of dapagliflozin on colistin-induced renal toxicity

  • Ejder Saylav Bora1
  • Mumin Alper Erdogan2
  • Ayfer Meral3
  • Zeynep Karakaya1
  • Oytun Erbas4

1İzmir Katip Çelebi University Atatürk Research and Training Hospital, Emergency Medicine, İzmir, Turkey

2İzmir Katip Çelebi University, Faculty of Medicine, Department of Physiology, Izmir, Turkey

3Van Yüzüncü Yıl University Department of Biochemistry Van, Turkey

4Demiroğlu Bilim University Depatment of Physiology Istanbul, Turkey

DOI: 10.22514/sv.2021.020 Vol.17,Issue 4,July 2021 pp.92-97

Submitted: 24 December 2020 Accepted: 15 January 2021

Published: 08 July 2021

*Corresponding Author(s): Ejder Saylav Bora E-mail: saylavbora@hotmail.com

Abstract

Objectives: Multiple-drug resistance to Gram-negative bacteria has increased signifi-cantly in recent years. Colistin is increasingly used as a last line of defense against these bacteria. However, colistin has been associated with nephrotoxicity in experimental animals. This study explores the protective effect of dapagliflozin in a rodent model of nephrotoxicity.

Material Method: The present study includes a total of 24 male rats, of which 16 were given a single 20 mg/kg dose of colistin (Colimycin 150 mg/mL) intravenously to induce renal toxicity. The remaining eight rats were given no drugs in order to serve as the control, Group A. The 16 rats treated with colistin were then divided into two groups. Rats in Group B received 0.9% NaCl saline solution at a dose of 30 mL/kg/day intraperitoneally (i.p.) and 10 mg/kg/day dapagliflozin (Forziga 10 mg) via oral gavage. Those in Group C received 0.9% NaCl saline solution at an i.p. dose of 30 mL/kg/day. Both saline and dapagliflozin were administered as described over the course of ten days. The animals were euthanized and blood samples were taken by cardiac puncture for further analysis. Their kidneys were removed for histopathological and biochemical examination.

Results: Levels of creatinine, BUN, KIM-1, and MDA were significantly increased in the 16-rat (Groups B and C) treatment group, in comparison to the control group; however, these biomarkers were significantly normalized in Group B, which had received dapagliflozin in addition to saline. The GSH levels of Group C showed significant decline when compared to those of the control group, and were significantly normalized in Group B. Histologically, in Group 2, we observed severe tubular dilatation and tubular epithelial cell injury in comparison to the control group. These severe anatomical changes were decreased in Group B.

Conclusion: Apart from its positive effect on glucose regulation, which is the usual purpose of dapagliflozin, we observed that in colistin-induced nephrotoxicity, it decreases oxidative stress by inhibiting SGLT-2, and has restorative effects in terms of histopathology and biochemistry. These findings offer hope that the use of dapagliflozin may be protective for contrast nephropathy, which causes renal tubule damage through oxidative mechanisms. Future studies will further clarify the mechanistic action of colistin and dapagliflozin, and may support the hypothesis that dapagliflozin can be used as an adjunctive therapy in all nephrotoxic conditions.


Keywords

Nephrotoxicity; Colistin; Dapagliflozin; Histopathology


Cite and Share

Ejder Saylav Bora,Mumin Alper Erdogan,Ayfer Meral,Zeynep Karakaya,Oytun Erbas. Protective effect of dapagliflozin on colistin-induced renal toxicity. Signa Vitae. 2021. 17(4);92-97.

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