A Comparative Study of the Nephroprotective Effects of Vildagliptin and Sitagliptin against Gentamicin-induced Nephrotoxicity in Rabbits

Authors

DOI:

https://doi.org/10.5281/zenodo.19864438

Keywords:

Nephrotoxicity, Gentamicin, Sitagliptin, Vildagliptin

Abstract

Objectives: This study aimed to compare the nephroprotective effects of sitagliptin and vildagliptin on gentamicin-induced nephrotoxicity in rabbits.

Materials and Methods: We divided 12 rabbits into four groups (3 per group): 1- Control group (saline only), 2- Diseased group (gentamicin only), 3- Treatment group I (sitagliptin + gentamicin), and 4- Treatment group II (vildagliptin + gentamicin). Serum creatinine was measured, and histopathological study was conducted.

Results: Gentamicin significantly elevated serum creatinine and induced inflammation and edema in renal cells. While both sitagliptin and vildagliptin mitigated nephrotoxicity, vildagliptin demonstrated better results, with significantly lower creatinine levels (p=0.000) and better renal histological improvement.

Conclusions: Vildagliptin exhibits stronger nephroprotective effects than sitagliptin against gentamicin-induced renal injury, likely due to its stronger anti-inflammatory properties. These results suggest that vildagliptin is preferable for patients at high risk of drug-induced nephrotoxicity, particularly those with diabetes.

Downloads

Download data is not yet available.

References

[1] L. Robson, “The kidney—an organ of critical importance in physiology,” The Journal of Physiology, vol. 592, no. 18, p. 3953, 2014.

[2] L. A. Stevens and A. S. Levey, “Measurement of kidney function,” Medical Clinics, vol. 89, no. 3, pp. 457–473, 2005.

[3] M. A. Perazella and M. H. Rosner, “Drug-induced acute kidney injury,” Clinical Journal of the American Society of Nephrology, vol. 17, no. 8, pp. 1220–1233, 2022.

[4] R. Bellomo, J. A. Kellum, and C. Ronco, “Acute kidney injury,” The Lancet, vol. 380, no. 9843, pp. 756–766, 2012.

[5] M. A. Gamaan, H. S. Zaky, and H. I. Ahmed, “Gentamicin-induced nephrotoxicity: A mechanistic approach,” Azhar International Journal of Pharmaceutical and Medical Sciences, vol. 3, no. 2, pp. 11–19, 2023.

[6] P. Randjelovic, S. Veljkovic, N. Stojiljkovic, D. Sokolovic, and I. Ilic, “Gentamicin nephrotoxicity in animals: Current knowledge and future perspectives,” EXCLI Journal, vol. 16, p. 388, 2017.

[7] N. Pannu and M. K. Nadim, “An overview of drug-induced acute kidney injury,” Critical Care Medicine, vol. 36, no. 4, pp. S216–S223, 2008.

[8] A. Ceriello, L. Sportiello, C. Rafaniello, and F. Rossi, “DPP-4 inhibitors: Pharmacological differences and their clinical implications,” Expert Opinion on Drug Safety, vol. 13, suppl. 1, pp. 57–68, 2014.

[9] E. E. Mulvihill and D. J. Drucker, “Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors,” Endocrine Reviews, vol. 35, no. 6, pp. 992–1019, 2014.

[10] S. A. Abuelezz, N. Hendawy, and S. Abdel Gawad, “Alleviation of renal mitochondrial dysfunction and apoptosis underlies the protective effect of sitagliptin in gentamicin-induced nephrotoxicity,” Journal of Pharmacy and Pharmacology, vol. 68, no. 4, pp. 523–532, 2016.

[11] R. E. Mostafa, A. H. Morsi, and G. F. Asaad, “Anti-inflammatory effects of saxagliptin and vildagliptin against doxorubicin-induced nephrotoxicity in rats: Attenuation of NLRP3 inflammasome up-regulation and tubulo-interstitial injury,” Research in Pharmaceutical Sciences, vol. 16, no. 5, pp. 547–558, 2021.

[12] S. M. Poucher, S. Cheetham, J. Francis, B. Zinker, M. Kirby, and S. P. Vickers, “Effects of saxagliptin and sitagliptin on glycaemic control and pancreatic β-cell mass in a streptozotocin-induced mouse model of type 2 diabetes,” Diabetes, Obesity and Metabolism, vol. 14, no. 10, pp. 918–926, 2012.

[13] T. Miyoshi, K. Nakamura, M. Yoshida, D. Miura, H. Oe, S. Akagi, and H. Ito, “Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats,” Cardiovascular Diabetology, vol. 13, pp. 1–10, 2014.

[14] K. Abu-Spetan and A. Abdel-Gayoum, “Effect of high dietary cholesterol on gentamicin-induced nephrotoxicity in rabbits,” Archives of Toxicology, vol. 75, pp. 284–290, 2001.

[15] J. M. Lopez-Novoa, Y. Quiros, L. Vicente, A. I. Morales, and F. J. Lopez-Hernandez, “New insights into the mechanism of aminoglycoside nephrotoxicity: An integrative point of view,” Kidney International, vol. 79, no. 1, pp. 33–45, 2011.

[16] D. Kawanami, Y. Takashi, H. Takahashi, R. Motonaga, and M. Tanabe, “Renoprotective effects of DPP-4 inhibitors,” Antioxidants, vol. 10, no. 2, p. 246, 2021.

[17] R. S. Abdelrahman, “Sitagliptin exerts anti-apoptotic effect in nephrotoxicity induced by cisplatin in rats,” Naunyn-Schmiedeberg’s Archives of Pharmacology, vol. 390, pp. 721–731, 2017.

[18] L. L. Glorie, A. Verhulst, V. Matheeussen, L. Baerts, J. Magielse, N. Hermans, and A. De Beuf, “DPP4 inhibition improves functional outcome after renal ischemia-reperfusion injury,” American Journal of Physiology-Renal Physiology, vol. 303, no. 5, pp. F681–F688, 2012.

[19] H. Ateyya, “Amelioration of cyclosporine induced nephrotoxicity by dipeptidyl peptidase inhibitor vildagliptin,” International Immunopharmacology, vol. 28, no. 1, pp. 571–577, 2015.

[20] H. E. S. Mostafa, E. A. Alaa El-Din, D. A. El-Shafei, N. S. Abouhashem, and A. A. Abouhashem, “Protective roles of thymoquinone and vildagliptin in manganese-induced nephrotoxicity in adult albino rats,” Environmental Science and Pollution Research, vol. 28, pp. 31174–31184, 2021.

[21] A. J. Scheen, “Pharmacokinetics of dipeptidylpeptidase-4 inhibitors,” Diabetes, Obesity and Metabolism, vol. 12, no. 8, pp. 648–658, 2010.

[22] R. Trevisan, “The role of vildagliptin in the therapy of type 2 diabetic patients with renal dysfunction,” Diabetes Therapy, vol. 8, no. 6, pp. 1215–1226, 2017.

[23] I. O. Sherif, A. A. Alshaalan, and N. H. Al-Shaalan, “Renoprotective effect of vildagliptin following hepatic ischemia/reperfusion injury,” Renal Failure, vol. 42, no. 1, pp. 208–215, 2020.

Downloads

Published

2024-12-15

Issue

Section

Articles - Volume 2 Number 2

Categories

How to Cite

[1]
A. . . Rastanawi, K. Krej, N. . Samsam, M. . . Kanjo, and M. . Al-shaqaqi, “A Comparative Study of the Nephroprotective Effects of Vildagliptin and Sitagliptin against Gentamicin-induced Nephrotoxicity in Rabbits”, J.W.P.U, vol. 2, no. 2, pp. 166–177, Dec. 2024, doi: 10.5281/zenodo.19864438.

Most read articles by the same author(s)

Similar Articles

You may also start an advanced similarity search for this article.