ANTIGENOTOXIC ACTIVITY OF THE COMBINATION «ASPARTAME + BETAINE» AND METFORMIN IN MICE WITH EXPERIMENTAL STREPTOZOTOCIN DIABETES

DOI: https://doi.org/10.29296/24999490-2022-05-08

A.A. Lisitsyn(1, 3), A.K. Zhanataev(1), Z.V. Chaika(1), E.M. Sevostyanova(2), M.P. Artamonova(3),
I.M. Chernukha(4), L.A. Oganesyants(2), A.D. Durnev(1),
1-V.V. Zakusov Research Institute of Pharmacology, Baltijskaya ul. 8, Moscow, 125315, Russian Federation;
2-All-Russian Research Institute of Brewing, Non-Alcoholic and Wine-making Industry – a branch of the Federal State
Budget Scientific Institution «V.M. Gorbatov Federal Research Center for Food Systems of RAS»,
ul. Rossolimo, 7, Moscow, 119021, Russian Federation;
3-Moscow State University of Food Production, Department of «Designing Functional Foods and Nutritionology»,
Volokolamskoe shosse, 11, Moscow, 125080, Russian Federation;
4-V.M. Gorbatov Federal Research Center for Food Systems of RAS, ul. Talalihina, 26, Moscow, 109316, Russian Federation

Introduction. An increase in DNA damage (genotoxicity) is characteristic of patients with diabetes mellitus. The main complications in diabetes are accompanied and/or initiated by DNA damage. Hence, the necessity to search for and study compounds with antigenotoxic properties for use in diabetes mellitus is obvious. Aim. Study of the antigenotoxic activity of aspartame and betaine combination in a mice diabetes mellitus model in comparison with the well-known hypoglycemic drug metformin. Material and methods. DNA damage was estimated using the «DNA comet» assay. Streptozotocin was used as a diabetogenic agent. Aspartame (35 mg/l) and betaine (175 mg/l) were given in the drinking water throughout the experiment. Metformin at a dose of 250 mg/kg was administered orally at the same time. The study was performed on BALB/c male mice. Results. After a single i.p. administration of 200 mg/kg streptozotocin or after its five-day daily administration at a dose of 40 mg/kg, hyperglycemia was observed, as well as DNA damage in the liver and kidney cells, but not in the brain, pancreas and testes cells. During the single streptozotocin injection experiment DNA damage under the influence of aspartame and betaine decreased by 58.0% in liver cells and by 53.8% in kidney cells. Metformin reduced DNA damage by 44.2 and 71.0%, respectively, in liver and kidney cells. During the repeated streptozotocin administration experiment aspartame and betaine reduced DNA damage by 52.2% in liver cells and by 46.6% in kidney cells. Metformin reduced DNA damage by 30.8 and 38.3%, respectively, in liver and kidney cells. Discussion. The data obtained demonstrate the antigenotoxic effect of the aspartame and betaine combination in experimental diabetes mellitus and confirm a similar activity in metformin, previously identified in a single study.
Keywords: 
diabetes, streptozotocin, aspartame, betaine, metformin, DNA damage, mice
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