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.