The Effect of the Chronic Administration of DPP4-Inhibitors on Systemic Oxidative Stress in Rats with Diabetes Type 2

Abstract

Type 2 diabetes (T2DM) is characterized by well-preserved insulin secretion; however, the surrounding tissue is insensitive to insulin, resulting in increased blood glucose level due to the inability of tissues to convert glucose into energy. As a result of chronic non-regulation of glucose levels and high daily fluctuations in the blood, the micro- and macrovascular complications occur in these patients. Complications develop through two main mechanisms: induction of oxidative stress and innate immunity. In this regard, the aim of this study was to examine the effect of four week administration of DPP4 inhibitors (saxagliptin, sitagliptin and vildagliptin) to the parameters of oxidative stress and antioxidant defense in the group of rats with diabetes type 2 (T2DM). Sixty Wistar albino rats were divided randomly into 5 groups: group I: control healthy group; group II: rats with diabetes type 2; group III: rats with diabetes type 2 treated with 0.6 mg/kg of sitagliptin; group IV: rats with diabetes type 2 treated with 0.45 mg/kg of saxagliptin, group V: rats with diabetes type 2 treated with 9 mg/kg vildagliptin. The rats from experimental groups were fed with a high-fat diet for 4 weeks and after 6–8 h of starvation received one dose of streptozotocin (STZ) intraperitoneally (25 mg/kg body weight) to induce T2DM. Animals with fasting glucose above 7 mmol / L and insulin over 6 mmol / L were included in the study as rats with T2DM. Upon completion of the experiments, the blood was collected from the anesthetized animals and used for sphectrophotometrical determination of parameters of oxidative stress, and antioxidative defense. T2DM induced significant increase in production of reacitve oxygen species (ROS) (superoxide anion radical and hydrogen peroxide), but additional four-week administration of gliptins induced decrease in ROS values. On the other hand, T2DM induced decrease of nitric oxide, superoxide dismutase, catalaze, and reduced gluthation and concomitant therapy with gliptins induced increase of these parametars, suggesting significant antioxidant potential of this group of drugs.

Targeting AGE‐RAGE signaling pathway by Saxagliptin prevents myocardial injury in isoproterenol challenged diabetic rats

“…These results align well with another study by Marques et al, 2019 in which Sitagliptin treatment ameliorated renal oxidative stress in rats with diabetes (Marques et al, 2019). Another study highlighted the anti-oxidant potential of gliptins, similar to this study (Bolevich et al, 2019). (Matsui, Nishino, Takeuchi, & Yamagishi, 2011).…”

The Safety and Efficacy of Combining Saxagliptin and Pioglitazone Therapy in Streptozocin-Induced Diabetic Rats

“…Moreover, Saxagliptin and Pioglitazone appear to have a synergistic effect on lipid profile improvement, as the best results were observed in the group that received combination therapy. In line with our findings, Saxagliptin was reported to improve dyslipidemia [45]. Pioglitazone has also been shown to improve lipid profiles [46].…”

“…Regarding oxidative stress, the effect of DPP-4 inhibitors and TZDs has been previously studied individually. One animal study reported similar results to our experiment, where three DPP-4 inhibitors, namely Saxagliptin, Sitagliptin, and Vildagliptin, were found to significantly reduce oxidative stress in STZ-induced diabetic rats [45]. Meanwhile, in a 16week clinical trial involving 40 patients with advanced diabetic nephropathy, Pioglitazone did not affect reducing oxidative stress [47].…”

“…Liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were measured with enzymatic colorimetric methods using Biodiagnostic kits, Egypt (Catalog No. AL 10 31 (45) and Catalog No. AS 10 61 (45), respectively).…”