Open AccessLong-term use of dipeptyl peptidase-4 inhibitors suppresses systemic oxidative stress in rats with type 2 diabetes
Author(s) -
Sergey Bolevich,
Петр Францевич Литвицкий,
Власов Борис Яковлевич,
Sergey Bolevich
Publication year - 2019
Publication title -
sečenovskij vestnik
Language(s) - English
Resource type - Journals
eISSN - 2658-3348
pISSN - 2218-7332
DOI - 10.47093/22187332.2019.4.21-30
Subject(s) - vildagliptin , superoxide dismutase , oxidative stress , chemistry , catalase , superoxide , reactive oxygen species , antioxidant , endocrinology , sitagliptin , medicine , glutathione , hydrogen peroxide , pharmacology , type 2 diabetes , biochemistry , diabetes mellitus , enzyme
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 inuence 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 (O 2 -), hydrogen peroxide (H 2 O 2 ), nitrite (NO 2 -), 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 signicant increase of reactive oxygen species (ROS): superoxide radical and hydrogen peroxide and to decrease in NO 2 -, reduced glutathione, catalase and SOD activity. Comparing groups 3–5 with group 2, treatment with DPP-4 inhibitors reduced excessive generation of superoxide radical (O 2 -) and hydrogen peroxide (H 2 O 2 ) (especially signicant in the group with vildagliptin) and increased the activity of catalase and superoxide dismutase (especially signicant 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 (NO 2 -) 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.