Long-term use of dipeptyl peptidase-4 inhibitors suppresses systemic oxidative stress in rats with type 2 diabetes

• Main Authors: S. S. Bolevich, P. F. Litvitsky, V. Jakovljevic, S. B. Bolevich
• Format: Article
• Language: Russian
• Published: Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University) 2019-12-01
• Series: Сеченовский вестник
• Subjects: type 2 diabetes mellitus; saxagliptine; sitagliptine; vildagliptine; oxidative stress; antioxidant defensive system
• Online Access: https://www.sechenovmedj.com/jour/article/view/179
• ISSN: 2218-7332; 2658-3348

Induction of oxidative stress is one of the main mechanisms responsible for the development of micro- and macrovascular angiopathy in patients with type 2 diabetes mellitus (DM-2).Aim. To evaluate the influence of long-term treatment with inhibitors of dipeptidyl peptidase-4 (DPP-4) on the characteristics of oxidative stress and the state of antioxidant defense system in rats with induced DM 2.Materials and methods. We divided 60 Wistar albino rats into 5 groups: group 1 (control) – normal animals; groups 2–5 rats with DM 2, induced by streptozotocin: group 2 – without treatment with DPP 4; group 3 – rats, treated with saxagliptin (0.45 mg/kg); group 4 – rats, treated with sitagliptin for 3 weeks (0.6 mg/kg); group 5 – rats, treated with vildagliptin (9 mg/kg). At the end of the experimental phase we determined the level of superoxide anion radical (O2-), hydrogen peroxide (H2O2), nitrite (NO2-), reduced glutathione, as well as the activity of catalase and superoxide dismutase (SOD) in the blood of rats using a diode array spectrophotometer.Results. Induction of DM-2 in experimental animals led to a significant increase of reactive oxygen species (ROS): superoxide radical and hydrogen peroxide and to decrease in NO2-, reduced glutathione, catalase and SOD activity. Comparing groups 3–5 with group 2, treatment with DPP-4 inhibitors reduced excessive generation of superoxide radical (O2-) and hydrogen peroxide (H2O2) (especially significant in the group with vildagliptin) and increased the activity of catalase and superoxide dismutase (especially significant in the group with v sitagliptin) but the normal values, received in group 1, were not reached. Treatment with all DPP-4 inhibitors brought the level of nitrite (NO2-) up to normal, comparable with group 1.Conclusions. DPP-4 inhibitors suppress systemic oxidative stress in rats with induced DM 2 via reduction of prooxidative molecules production and activation of antioxidant defensive system.