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Sitagliptin exerts anti-apoptotic effect in nephrotoxicity induced by cisplatin in rats

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Abstract

Sitagliptin is a selective inhibitor of dipeptidylpeptidase-4 enzyme used for the management of diabetes mellitus type II. The anti-inflammatory, antioxidant, and anti-apoptotic properties of sitagliptin were documented. This study was designed to explore the effect of sitagliptin (10 mg/kg, orally) on nephrotoxicity induced by cisplatin (7 mg/kg, i.p.) in Sprague-Dawley rats. Nephrotoxicity of cisplatin was manifested by elevation in renal somatic index, proteinuria, blood urea nitrogen, creatinine in serum, lactate dehydrogenase, kidney malondialdehyde, NF-κB, Bax, and annexin V. Furthermore, body weight, serum albumin, nitric oxide, creatinine clearance, and the renal antioxidant defense system were significantly decreased by cisplatin. Sitagliptin administration ameliorated cisplatin-induced changes in kidney function, oxidative stress, inflammation, and apoptosis parameters. Improvement in both morphological examination of kidney and the urinary bladder response to acetylcholine supported these results. These findings indicated that sitagliptin, through its anti-inflammatory, anti-apoptotic, and antioxidant effects, can be used as a nephroprotectant against nephrotoxicity induced by cisplatin.

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Abbreviations

Cis:

Cisplatin

Sita:

Sitagliptin

Cr:

Creatinine

NF-κB:

Nuclear factor kappa-B

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Acknowledgments

The author acknowledges Dr. Mohamed F. Hamed, “Department of Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt,” for providing assistance in the histopathological examination. In addition, the author thanks Dr. Mona S Gouida, “Assistant Consultant of Molecular Immunology, Genetics Unit, Head of Flow Cytometry Unit, Mansoura Children Hospital,” for providing assistance in flow cytometry technique.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt

    Rehab S. Abdelrahman

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  1. Rehab S. Abdelrahman
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Correspondence to Rehab S. Abdelrahman.

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All procedures have been approved by the “Research Ethics Committee of Faculty of Pharmacy, Mansoura University, Egypt” which is in accordance with Laboratory Animal Care (NIH publication no. 85-23).

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The authors declare that they have no conflict of interest.

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Abdelrahman, R.S. Sitagliptin exerts anti-apoptotic effect in nephrotoxicity induced by cisplatin in rats. Naunyn-Schmiedeberg's Arch Pharmacol 390, 721–731 (2017). https://doi.org/10.1007/s00210-017-1367-2

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  • DOI: https://doi.org/10.1007/s00210-017-1367-2

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