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Validity of the Models of Experimental Diabetes for Oxidative Stress Studies. P. 66–78

Версия для печати

Section: Medical and biological sciences

UDC

616.379-008.64-092.11

DOI

10.17238/issn2542-1298.2019.7.1.66

Authors

Mariya I. Yashanova*, Tat’yana G. Shcherbatyuk*, Vadim Yu. Nikolaev**
*Privolzhsky Research Medical University (Nizhny Novgorod, Russian Federation)
**Nizhny Novgorod State Agricultural Academy (Nizhny Novgorod, Russian Federation)

Abstract

Oxidative stress plays an important role in the pathogenesis of diabetes mellitus (DM) and the development of its complications. It was not until fairly recently that DM began to be studied as a freeradical pathology. Thus, there are currently no unified methodological approaches to assessing the effect of oxidative stress on the pathogenesis of DM and to analysing the effectiveness of antioxidant therapy. For this reason, new models are required for assessing the antioxidant effect of new drugs. We performed a comparative analysis of the activity of free-radical processes in 49 white outbred male rats with diabetes induced by intraperitoneal injection of alloxan (120 mg/kg) and streptozotocin (40 mg/kg), the latter preceded by a high-calorie diet (STZ DM). The research found that the formation of lipid and protein oxidation products is more intensive in rats with STZ DM than in those with alloxan-induced DM. Moreover, animals with experimental STZ DM stay alive longer, which makes it possible to use this model in evaluating long-term effects of various drugs. In order to estimate the validity of the STZ DM model for oxidative stress studies, saxagliptin (Onglyza) at a dosage of 3 mg/kg was administered by intragastric gavage for 14 days to animals with STZ DM (10 rats). After 14 days of administration, the drug decreased the total free-radical activity, concentration of malondialdehyde and all products of oxidative modification of proteins during spontaneous oxidation, which proves that the STZ DM model can be used to evaluate the antioxidant effect of antidiabetic drugs.

Keywords

experimental diabetes, alloxan, streptozotocin, oxidative modification of proteins and lipids, ketone-dinitrophenylhydrazones, aldehydе-dinitrophenylhydrazones, malondialdehyde, saxagliptin
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References

1. IDF DIABETES Atlas. 8th ed. 2017. Available at: http://www.diabetesatlas.org/resources/2017-atlas.html (accessed: 21 December 2018).
2. Balabolkin M.I., Klebanova E.M., Kreminskaya V.M. Primenenie ubikhinona (koenzima Q) v kompleksnoy terapii sakharnogo diabeta i ego sosudistykh oslozhneniy [The Use of Ubiquinone (Coenzyme Q) in the Complex Therapy of Diabetes Mellitus and Its Vascular Complications]. Sakharnyy diabet, 2007, no. 4, pp. 37–42.
3. Lankin V.Z., Tikhaze A.K., Kumskova E.M. Osobennosti modifikatsii lipoproteinov nizkoy plotnosti v razvitii ateroskleroza i sakharnogo diabeta tipa 2 [Modification of Low-Density Lipoproteins in the Development of Atherosclerosis and Type 2 Diabetes Mellitus]. Kardiologicheskiy vestnik, 2008, vol. 3, no. 1, pp. 60–67.
4. Brownlee M. Biochemistry and Molecular Cell Biology of Diabetic Complications. Nature, 2001, vol. 414, no. 6865, pp. 813–820.
5. Sorokina Yu.A., Lovtsova L.V., Bogdarina A.V., Yashanova M.I., Shcherbatyuk T.G. Sinergizm pri kombinirovannom ispol’zovanii peroral’nykh sakharosnizhayushchikh preparatov [Synergism in Combined Use of Oral Antihyperglycemic Drugs]. Sovremennye tekhnologii v meditsine, 2014, vol. 6, no. 3, pp. 85–90.
6. Lenzen S. The Mechanisms of Alloxan- and Streptozotocin-Induced Diabetes. Diabetologia, 2008, vol. 51, no. 2, pp. 216–226.
7. Pal’chikova N.A., Kuznetsova N.V., Kuz’minova O.I., Selyatitskaya V.G. Gormonal’no-biokhimicheskie osobennosti alloksanovoy i streptozototsinovoy modeley eksperimental’nogo diabeta [Hormonal and Biochemical Features of Alloxan- and Streptozotocin-Induced Models of Experimental Diabetes]. Byulleten’ SO RAMN, 2013, vol. 33, no. 6, pp. 18–24.
8. Spasov A.A., Voronkova M.P., Snigur G.L., Cheplyaeva N.I., Chepurnova M.V. Eksperimental’naya model’ sakharnogo diabeta tipa 2 [Experimental Model of Type 2 Diabetes]. Biomeditsina, 2011, no. 3, pp. 12–19.
9. Islam M.S., Choi H. Nongenetic Model of Type 2 Diabetes: A Comparative Study. Pharmacology, 2007, vol. 79, no. 4, pp. 243–249.
10. Bayrasheva V.K., Babenko A.Yu., Dmitriev Yu.V., Bayramov A.A., Chefu S.G., Shatalov I.S., Pchelin I.Yu., Ivanova A.N., Grineva E.N. Novaya model’ sakharnogo diabeta 2-go tipa i diabeticheskoy nefropatii u krys [A Novel Model of Type 2 Diabetes and Diabetic Nephropathy in Rats]. Translyatsionnaya meditsina, 2016, vol. 3, no. 4, pp. 44–55.
11. Baranov V.G., Sokoloverova I.M., Gasparyan E.G., et al. Eksperimental’nyy sakharnyy diabet. Rol’ v klinicheskoy diabetologii [Experimental Diabetes: Its Role in Clinical Diabetology]. Leningrad, 1983. 238 p.
12. Mironov A.N. (ed.). Rukovodstvo po provedeniyu doklinicheskikh issledovaniy lekarstvennykh sredstv [Guidelines for Conducting Preclinical Studies on Drugs]. Pt. 1. Moscow, 2012. 944 p.
13. Shcherbatyuk T.G. Svobodnoradikal’nye protsessy i ikh korrektsiya u zhivotnykh s eksperimental’nymi opukholyami [Free-Radical Processes and Their Correction in Animals with Experimental Tumours]. Nizhny Novgorod, 2003. 315 p.
14. Kuz’mina E.I., Nelyubin A.S., Shchennikova M.K. Primenenie indutsirovannoy khemilyuminestsentsii dlya otsenok svobodnoradikal’nykh reaktsiy v biologicheskikh substratakh [The Use of Induced Chemiluminescence for Evaluation of Free-Radical Reactions in Biological Substrates]. Biokhimiya i biofizika mikroorganizmov [Microbial Biochemistry and Biophysics]. Gorky, 1983, pp. 179–183.
15. Arutyunyan A.V., Dubinina E.E., Zybina N.N. Metody otsenki svobodnoradikal’nogo okisleniya i antioksidantnoy sistemy organizma [Methods for Evaluating Free-Radical Oxidation and the Body’s Antioxidant System]. St. Petersburg, 2000. 104 p.
16. Nishikimi M., Appaji Rao N., Yagi K. The Occurrence of Superoxide Anion in the Reaction of Reduced Phenazine Methosulfate and Molecular Oxygen. Biochem. Biophys. Res. Commun., 1972, vol. 46, no. 2, pp. 849–854.
17. Aebi H. Catalase in vitro. Methods Enzymol., 1984, vol. 105, pp. 121–126.
18. Yan’kova V.I., Ivanova I.L., Fedoreev S.A., Kulesh N.I. Antioksidantnoe deystvie gepatoprotektora maksara pri eksperimental’nom diabete [Antioxidant Activity of the Hepatoprotector Maxar in Experimental Diabetes]. Eksperimental’naya i klinicheskaya farmakologiya, 2002, vol. 65, no. 4, pp. 33–36.
19. Zolotareva S.N., Mubarakshina O.A. Okislitel’nyy stress i antioksidantnyy status pri eksperimental’nom alloksanovom diabete [Oxidative Stress and Antioxidant Status in Alloxan-Induced Experimental Diabetes]. Svobodnye radikaly, antioksidanty i zdorov’e zhivotnykh [Free Radicals, Antioxidants and Animal Health]. Voronezh, 2004, pp. 47–52.
20. Savchenko A.A., Titova N.M., Subbotina T.N., Gershkoron F.A., Manchuk V.T., Al’brant E.V. Rol’ svobodnoradikal’nykh i metabolicheskikh protsessov v patogeneze sakharnogo diabeta I tipa [The Role of Free-Radical and Metabolic Processes in the Pathogenesis of Type 1 Diabetes]. Krasnoyarsk, 2012. 269 p.
21. Kolesnikova L.I., Vlasov B.Ya., Kolesnikov S.I., Darenskaya M.A., Grebenkina L.A., Semenova N.V., Vanteeva O.A. Intensity of Oxidative Stress in Mongoloid and Caucasian Patients with Type 1 Diabetes Mellitus. Bull. Exp. Biol. Med., 2016, vol. 161, no. 6, pp. 767–769.
22. Dubinina E.E. Produkty metabolizma kisloroda v funktsional’noy aktivnosti kletok (zhizn’ i smert’, sozidanie i razrushenie) [Oxygen Metabolism Products in the Functional Activity of Сells (Life and Death, Creation and Destruction)]. St. Petersburg, 2006. 397 p.
23. Kosenko E.A., Kaminskiy A.Yu., Kaminskiy Yu.G. Aktivnost’ antiokislitel’nykh fermentov v pecheni i mozge snizhaetsya v rannie sroki diabeta, i eto snizhenie zavisit ot funktsionirovaniya NMDA-retseptorov [The Activity of Antioxidant Enzymes in the Liver and the Brain Decreases at the Early Stages of Diabetes, and This Decrease Depends on the Functioning of NMDA Receptors]. Voprosy meditsinskoy khimii, 1999, vol. 45, no. 4, pp. 304–308.
24. Kakkar R., Kalra J., Mantha S.V., Prasad K. Lipid Peroxidation and Activity of Antioxidant Enzymes in Diabetic Rats. Mol. Cell. Biochem., 1995, vol. 151, no. 2, pp. 113–119.
25. Mkrtumyan A.M. Saksagliptin otkryvaet novye vozmozhnosti effektivnogo i bezopasnogo kontrolya glikemii u bol’nykh sakharnym diabetom tipa 2 [Saxagliptin Opens New Opportunities for Effective and Safe Glycemic Control in Patients with Type 2 Diabetes Mellitus]. Farmateka, 2010, no. 16, pp. 32–36.
26. Solini A., Rossi C., Duranti E., Taddei S., Natali A., Virdis A. Saxagliptin Prevents Vascular Remodeling and Oxidative Stress in db/db Mice. Role of Endothelial Nitric Oxide Synthase Uncoupling and Cyclooxygenase. Vascul. Pharmacol., 2016, vol. 76, pp. 62–71.



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