Sitagliptin mitigated cyclosporine-induced renal oxidative stress, apoptosis and histopathological alterations

Makram, Sohyla Mahmoud; Shehata, Basim Anwar; Abdelhafeez, Hanan Hassan; Abdel-dayem, Ahmed Mohammed

doi:10.21608/mermj.2025.333439.1020

Sitagliptin mitigated cyclosporine-induced renal oxidative stress, apoptosis and histopathological alterations

Document Type : Original Article

Authors

¹ demonstrator of Pharmacology, faculty of medicine, Merit Univesity, Egypt

² professor of Pharmacology and toxicology, faculty of pharmacy, beni-suef Univesity, Egypt

³ department of cell and tissue faculty of veterinary medicine assuit university

⁴ associated professor of Pharmacology Dep, Faculty of medicine, Assiut university

10.21608/mermj.2025.333439.1020

Abstract

ABSTRACT
Aim: Cyclosporine A (CsA) nephrotoxicity is a serious problem in modern immunosuppressive regimens. Sitagliptin, an antidiabetic, has been investigated for its antioxidant, anti-inflammatory, and tissue-protective features. We intended to study the possible nephroprotective benefits of sitagliptin against cyclosporine and elucidate the mechanisms that underlie these benefits.
Methods: Male adult rats have been divided into four groups: Group 1 (control) rats received the vehicle; Group 2 rats received cyclosporine (CsA); Group 3 rats were given sitagliptin; and Group 4 rats were given both CsA and sitagliptin. The blood urea, creatinine and cystatin-C (CYS-C) levels were tested. The renal malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) levels were determined. A histopathological analysis of kidney tissues and an immunostaining investigation of Bax and Nrf-2 were performed.
Results: We found that sitagliptin mitigated CsA-mediated increases in serum urea, creatinine, cystatin-C, and renal MDA while inhibiting CsA-induced reductions in renal CAT, SOD, and GSH. It combated both the increased expression of renal Bax, and the degenerative kidney tissue damage caused by CsA. Furthermore, Nrf2 expression levels in the kidney were dramatically elevated.
Conclusion: Sitagliptin could protect the kidney from CsA's detrimental impacts by reducing inflammation, oxidative stress, and apoptosis while also increasing antioxidant mechanisms.

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