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The Effect of the Dipeptidyl Peptidase‐4 Inhibitor Sitagliptin on Gentamicin Nephrotoxicity in Mice
Author(s) -
Ali Badreldin H.,
Suleimani Yousuf M.,
Abdelrahman Aly M.,
Karaca Turan,
Nemmar Abderrahim
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.562.2
Subject(s) - sitagliptin , nephrotoxicity , creatinine , dipeptidyl peptidase 4 inhibitor , medicine , endocrinology , gentamicin , oxidative stress , chemistry , pharmacology , kidney , metformin , diabetes mellitus , antibiotics , biochemistry , type 2 diabetes
This study aimed at investigating the possible ameliorative effects of sitagliptin in mice with gentamicin (GEN) nephrotoxicity. Sitagliptin was given to the animals at an oral dose of 10 mg kg −1 per day for 10 days, and in some of these mice, GEN was injected intraperitoneally at a dose of 100 mg kg −1 per day during the last seven days of the treatment. Nephrotoxicity was evaluated histopathologically by light microscopy and biochemically by measuring several indices in plasma, urine and renal cortex homogenates. GEN treatment induced nephrotoxicity as evidenced by significantly ( P <0.0001) increasing the plasma concentrations of urea, creatinine, circulatory cytokines, cystatin C, sclerostin, and TNFα. Treatment with GEN also significantly elevated urinary N ‐acetyl‐β‐D glucosaminidase (NAG) concentration ( P <0.0001). Moreover, GEN caused significant increase in oxidative stress in the kidneys ( P <0.0001). Histopathological examination revealed massive tubular injury, necrosis, infiltration of inflammatory cells and intraluminal hyaline casts in mice treated with GEN. Sitagliptin alone did not significantly affect any of the indices measured. However, concomitant treatment with sitagliptin and GEN significantly mitigated most of the nephrotoxic actions of GEN. Pending further studies, sitagliptin may potentially be useful as a nephroprotectant agent. Support or Funding Information This work was financially supported by a grant from SQU, Oman (IG/MED/PHAR/17/1) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .