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

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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.

About the Authors

S. S. Bolevich
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Stefani S. Bolevich, Assistant Professor at the Pathophysiology Department

8/2 Trubetskaya st., Moscow, 119991
Tel.: +7 (903) 787-44-66 

P. F. Litvitsky
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Petеr F. Litvitsky, Doctor of Medical Science, Professor,  Corresponding member of RAS, Head of the Pathophysiology Department


V. Jakovljevic
University of Kragujevac

Vladimir Jakovljevic, MD, Professor, Dean of the Faculty of Medical Sciences


S. B. Bolevich
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Sergey B. Bolevich, Doctor of Medical Science, Professor, Head of the Human Pathology Department



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