Ameliorative potential of sitagliptin and/or resveratrol on experimentally-induced clear cell renal cell carcinoma

Abstract

The aim of this study was to assess the effect of sitagliptin with or without resveratrol on carcinogen-induced clear cell renal cell carcinoma. Sixty male Wistar rats were divided into 6 equal groups as follows: control; clear cell renal cell carcinoma group; clear cell renal cell carcinoma+sitagliptin group; clear cell renal cell carcinoma+resveratrol group; clear cell renal cell carcinoma+carboxymethyl cellulose group and clear cell renal cell carcinoma+sitagliptin+resveratrol group. Blood urea, serum creatinine, creatinine clearance, urinary N-acetyl beta-d-glucosaminidase (NAG), gamma glutamyl transpeptidase (GGT) and urinary albumin excretion rate (UAER) were determined. Renal tissue antioxidant enzymes, lactate dehydrogenase (LDH), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), transforming growth factor beta-1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and signal transducers and activators of transcription-3 (STAT3) were determined. Parts of the kidneys were subjected to histopathological and immunohistochemical examination for nuclear factor kappa B (p65). Sitagliptin and/or resveratrol induced significant improvement of the renal functions with significant increase in tissue antioxidant defenses and Nrf2/HO-1 content associated with significant decrease in tissue LDH, TGF-β1, TNF-α, IL-6 and STAT3 and alleviated the histopathological and immunohistochemical changes compared to the untreated clear cell renal cell carcinoma group. These effects were significant in sitagliptin/resveratrol combination group compared to the use of each of these drugs alone. In conclusion, sitagliptin/resveratrol combination might represent a beneficial therapeutic modality for amelioration of experimentally-induced clear cell renal cell carcinoma.

Keywords: Clear cell; Rats; Renal cell carcinoma; Resveratrol; Sitagliptin.