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Research Article

Liraglutide Attenuates Gentamicin-Induced Nephrotoxicity in Rats by Reducing Oxidative Stress


1 Urology Department, Sakarya University Training and Research Hospital, Sakarya, Türkiye
2 Department of Urology, Basaksehir Cam and Sakura City Hospital, Istanbul, Türkiye
3 Department of Pathology, Istanbul University-Cerrahpasa, Faculty of Veterinary Medicine, Istanbul, Türkiye
4 Department of Medical Biochemistry, Kocaeli University, Faculty of Medicine, Kocaeli, Türkiye
5 Department of Urology, University of Health Sciences Okmeydani Training and Research Hospital, Istanbul, Türkiye


DOI : 10.33719/nju1447326
New J Urol. 2024;19(2):68-77.

Abstract

Objective: Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe Gram-negative infections. As we know, treatment with liraglutide has been shown to reduce oxidative stress. Therefore, we evaluated the potential protective effect of liraglutide against GEN-induced nephrotoxicity in rats.
Material And Methods: Twenty-eight rats were randomly divided into four groups: control group (Group 1); rats intraperitoneally injected with GEN (100 mg/kg/day; Group 2); rats treated with GEN plus distilled water (Group 3); and rats treated with GEN plus liraglutide (0.6 mg/kg/day; Group 4). After 15 days, the rats were sacrificed, their kidneys taken, and blood analysis performed. Tubular necrosis, interstitial fibrosis, and inducible nitric oxide synthetase (iNOS) scores were determined histopathologically in a part of the kidneys; malondialdehyde (MDA), reduced glutathione (GSH), E-cadherin and transforming growth factor β1 (TGF-β1) levels were determined in another part of kidneys. 
Results: The GSH levels in renal tissue of only GEN-treated rats were significantly lower than others, and the administration of liraglutide to rats significantly increased the level of GSH. The group that was given GEN plus liraglutide had significantly lower MDA, TGF - β1, and E - cadherin levels than that given GEN alone. The rats treated with GEN+liraglutide indicated less severe tubular necrosis and their glomeruli maintained a better morphology compared to the GEN group. iNOS expression was higher in the liraglutide administrated group than the group that applied only GEN.
Conclusion: Liraglutide exerts protective effects on GEN-induced kidney damage by reducing oxidative stress in rat model.

Keywords: gentamicin, liraglutide, kidney


Abstract

Objective: Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe Gram-negative infections. As we know, treatment with liraglutide has been shown to reduce oxidative stress. Therefore, we evaluated the potential protective effect of liraglutide against GEN-induced nephrotoxicity in rats.
Material And Methods: Twenty-eight rats were randomly divided into four groups: control group (Group 1); rats intraperitoneally injected with GEN (100 mg/kg/day; Group 2); rats treated with GEN plus distilled water (Group 3); and rats treated with GEN plus liraglutide (0.6 mg/kg/day; Group 4). After 15 days, the rats were sacrificed, their kidneys taken, and blood analysis performed. Tubular necrosis, interstitial fibrosis, and inducible nitric oxide synthetase (iNOS) scores were determined histopathologically in a part of the kidneys; malondialdehyde (MDA), reduced glutathione (GSH), E-cadherin and transforming growth factor β1 (TGF-β1) levels were determined in another part of kidneys. 
Results: The GSH levels in renal tissue of only GEN-treated rats were significantly lower than others, and the administration of liraglutide to rats significantly increased the level of GSH. The group that was given GEN plus liraglutide had significantly lower MDA, TGF - β1, and E - cadherin levels than that given GEN alone. The rats treated with GEN+liraglutide indicated less severe tubular necrosis and their glomeruli maintained a better morphology compared to the GEN group. iNOS expression was higher in the liraglutide administrated group than the group that applied only GEN.
Conclusion: Liraglutide exerts protective effects on GEN-induced kidney damage by reducing oxidative stress in rat model.

Keywords: gentamicin, liraglutide, kidney