Sitagliptin or Hesperidin Mitivates Cyclosporine-Induced Nephrotoxicity by Inhibiting Oxidative Stress and Apoptosis

Abstract Background and aims: Immunosuppressive medication Cyclosporine A (CsA) is frequently used during organ transplantation. Additionally, rheumatoid arthritis and other autoimmune diseases have been treated with CsA. But it causes nephrotoxicity. Sitagliptin is a DPP-4 inhibitor that has been approved for the treatment of type 2 diabetes in adults. It is very effective. Citrus fruits contain the flavonone hesperidin, which is highly effective in treating a number of cardiovascular disorders. The study's goal was to clarify how sitagliptin or hesperidin prevented CsA's nephrotoxic effects. Main methods: This study was done on 36 rats. The experimental design was designed into 6 groups that includes Group І (normal control): Rats received vehicle only for 14 days. Group ІІ: Rats injected with a single daily i.p 20 mg/kg/day dosage CsA for the last 7 consecutive days. Group ІІІ: Sitagliptin was administered orally to rats once daily for 14 days at a dose of 10 mg/kg. Group ІV: Rats received both CsA and sitagliptin treatments as previously indicated. Sitagliptin was administered 7 days before and 7 days after CsA that was administrated last 7 days. Group V: For 14 days straight, rats were given a single 200 mg/kg oral dosage of hesperidin formulated in distal water by oral gavage and Group VІ: Rats received both CsA and hesperdin treatments as previously indicated. Blood and kidneys were taken on day 15. In addition to a histological analysis, markers of renal function, oxidative stress, inflammation and apoptosis were measured. Results: Interestingly, sitagliptin or hesperidin attenuated CsA-mediated elevations of creatinine, Cystatin-C, glucose, MDA and MPO, while inhibiting CsA-induced decreases in albumin, catalase and GSH. Immunogenic assay of Nrf-2 and BAX and determination of tumor necrosis factor α (TNF-α) and western plot analysis among different groups also confirmed the safeguarding impact of sitagliptin or hesperidin on CsA-induced nephrotoxicity. Further confirmation of the reno-protective milieu provided by sitagliptin or hesperidin came from histological investigation. Conclusion: our findings suggested that sitagliptin or hesperidin treatment along with CsA lowers CsA's nephrotoxicity, possibly acting by inhibiting oxidative stress, inflammation and apoptosis.