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

https://doi.org/10.47093/22187332.2019.4.21-30

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Abstract

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

Moscow



V. Jakovljevic
University of Kragujevac

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

Kragujevac



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

Moscow



References

1. Dedov I.I. Saharnyj diabet tipa 2. Ot teorii k praktike. / Type 2 diabetes mellitus: from theory to practice. Moscow: MIA, 2016; 576p. [in Russian]. ISBN 978-5-9986-0248-1.

2. Dedov I.I., Shestakova M.V., Vikulova O.K. Epidemiologiia sakharnogo diabeta v Rossiiskoi Federatsii: kliniko-statisticheskii analiz po dannym Federal'nogo registra sakharnogo diabeta. | Epidemiology of diabetes mellitus in Russian Federation: clinical and statistical report according to the federal diabetes registry. Diabetes Mellitus. 2017; 20 (1): 13–41. [in Russian]. DOI: 10.14341/DM8664.

3. Filippas-Ntekouan S, Filippatos TD, Elisaf MS. SGLT2 inhibitors: are they safe? Postgrad Med. 2018; 130 (1): 72-82. DOI: 10.1080/00325481.2018.1394152. PMID: 29039237.

4. Dedov I.I., Shestakova M.V. Oslozhnenija saharnogo diabeta. Lechenie i profilaktika. / Complications of diabetes. Treatment and prevention. Moscow: MIA, 2017; 744. [in Russian]. ISBN 978-5-9986-0300-6.

5. Rumyantceva S.A., Silina E.V., Orlova A.S. et al. Giperglikemiia i svobodnoradikal'nyi disbalans kak prognosticheskie markery ostrogo narusheniia mozgovogo krovoobrashcheniia. / Hyperglycemia and free radical imbalance as prognostic factors of stroke. Annaly klinicheskoj i eksperimental'noj nevrologii. 2012; 6 (4): 26-9. [in Russian].

6. Sani NF, Belani LK, Sin CP et al. Effect of the combination of gelam honey and ginger on oxidative stress and metabolic profile in streptozotocin-induced diabetic Sprague-Dawley rats. Biomed Res Int. 2014: 160695. DOI: 10.1155/2014/160695. PMID: 24822178.

7. Gupta V, Kalra S. Choosing a gliptin. Indian J Endocrinol Metab. 2011; 15: 298–308. DOI: 10.4103/2230-8210.85583. PMID: 22029001

8. Tatosian DA, Guo Y, Schaeffer AK, et al. Dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes treated with saxagliptin, sitagliptin, or vildagliptin. Diabetes Ther. 2013 Dec; 4 (2): 431-42. DOI: 10.1007/s13300-013-0045-8. PMID: 24163113

9. Jakovljevic V, Milic P, Bradic J, et al. Standardized Aronia melanocarpa Extract as Novel Supplement against Metabolic Syndrome: A Rat Model. Int J Mol Sci. 2018 Dec 20; 20 (1): 6. DOI: 10.3390/ijms20010006. PMID: 30577476.

10. Hulman A., Vistisen D., Glümer C. et al. Glucose patterns during an oral glucose tolerance test and associations with future diabetes, cardiovascular disease and all-cause mortality rate. Diabetologia. 2018. Vol. 61 (1): 101–7. DOI: 10.1007/s00125-017-4468-z. PMID: 28983719.

11. Zheng Y., Ley S., Hu F. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nature Reviews Endocrinology. 2018. Vol. 14 (2): 88–98. DOI: 10.1038/nrendo.2017.151. PMID: 29219149.

12. Rehman K, Akash MSH. Mechanism of Generation of Oxidative Stress and Pathophysiology of Type 2 Diabetes Mellitus How Are They Interlinked? J Cell Biochem. 2017; 118 (11) :3577-85. DOI:10.1002/jcb.26097

13. Breitzig M, Bhimineni C, Lockey R, Kolliputi N. 4-Hydroxy-2-nonenal: a critical target in oxidative stress? Am J Physiol Cell Physiol. 2016 Oct 1; 311 (4): C537-C543. DOI: 10.1152/ajpcell.00101.2016

14. Nowotny K, Jung T, Höhn A, et al. Advanced glycation end productsand oxidative stress in type 2 diabetes mellitus, Biomolecules. 2015; 5 (1): 194-222. DOI: 10.3390/biom5010194.

15. Pеrez-Matute P, Zulet MA, Martínez JA. Reactive species and diabetes: counteracting oxidative stress to improve health. Curr Opin Pharmacol. 2009; 9 (6): 771-9. DOI: 10.1016/j.coph.2009.08.005.

16. Murakami K, Kondo T, Ohtsuka Y. et al. Impairment of glutathione metabolism in erythrocytes from patients with diabetes mellitus. Metabolism. 1989; 38 (8): 753-8. DOI: 10.1016/0026-0495(89)90061-9. PMID: 2569661

17. Kottenberg E, Thielmann M, Kleinbongard P, et al. Myocardial protection by remote ischaemic pre-conditioning is abolished in sulphonylurea-treated diabetics undergoing coronary revascularisation. ActaAnaesthesiol Scand. 2014; 58 (4): 453-62. DOI: 10.1111/aas.12278. PMID: 24548338.

18. Tatosian DA, Guo Y, Schaeffer AK, et al. Dipeptidyl peptidase-4 inhibition in patients with type 2 diabetes treated with saxagliptin, sitagliptin, or vildagliptin. Diabetes Therapy. 2013; 4 (2): 431-42. DOI:10.1007/s13300-013-0045-8

19. Sherif IO, Al-Shaalan NH. Vildagliptin Attenuates Hepatic Ischemia/Reperfusion Injury via the TLR4/NF-κB Signaling Pathway. Oxid Med Cell Longev. 2018: 3509091. DOI:10.1155/2018/3509091. PMID: 30405876.

20. El-Kashef DH, Serrya MS. Sitagliptin ameliorates thioacetamide-induced acuteliver injury via modulating TLR4/NF-KB signaling pathway in mice. Life Sci. 2019; 228: 266-273. DOI:10.1016/j.lfs.2019.05.019.

21. Sangle G., Patil M., Deshmukh N. et al. Evaluation of pharmacokinetic and pharmacodynamic parameters following single dose of sitagliptin in healthy Indian males. European journal of clinical pharmacology. 2018. Vol. 74 (5): 561–569. DOI: 10.1007/s00228-018-2433-5.

22. Trocha M, Krzystek-Korpacka M, Merwid-Ląd A, et al. Sitagliptin-Dependent Differences in the Intensity of Oxidative Stress in Rat Livers Subjected to Ischemia and Reperfusion. Oxid Med Cell Longev. 2019 Oct 31: 2738605. DOI:2019:2738605. PMID: 31781329

23. Refaat R, Sakr A, Salama M, El Sarha A. Combination of Vildagliptin and Pioglitazone in Experimental Type 2 Diabetes in Male Rats. Drug Dev Res. 2016; 77 (6) :300-9. DOI:10.1002/ddr.21324.

24. Helal MG, Zaki MMAF, Said E. Nephroprotective effect of saxagliptin againstgentamicin-induced nephrotoxicity, emphasis on anti-oxidant, anti-inflammatoryand anti-apoptic effects. Life Sci. 2018; 208 : 64-71. DOI:10.1016/j.lfs.2018.07.021.


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ISSN 2218-7332 (Print)
ISSN 2658-3348 (Online)