Antigenotoxic activity of the combination «aspartame + betaine» and metformin in mice with experimental streptozotocin diabetes

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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.

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作者简介

Artem Lisitsyn

V.V. Zakusov Research Institute of Pharmacology; Moscow State University of Food Production

编辑信件的主要联系方式.
Email: nordikal@yandex.ru

Junior Researcher; Postgraduate student; Department of «Designing Functional Food Products and Nutritionology»

Baltijskaya ul. 8, Moscow, 125315, Russian Federation; Volokolamskoe shosse, 11, Moscow, 125080, Russian Federation

Aliy Zhanataev

V.V. Zakusov Research Institute of Pharmacology

Email: zhanataev@academpharm.ru
leading researcher; Candidate of Biological Science Baltijskaya ul. 8, Moscow, 125315, Russian Federation

Zlata Chaika

V.V. Zakusov Research Institute of Pharmacology

Email: pcr201069@yandex.ru
researcher Baltijskaya ul. 8, Moscow, 125315, Russian Federation

Elena Sevostyanova

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»

Email: waterlena@list.ru
leading researcher; Candidate of Biological Science. ul. Rossolimo, 7, Moscow, 119021, Russian Federation

Marina Artamonova

Moscow State University of Food Production

Email: artamonovamp@mgupp.ru
Associate Professor; Department of «Designing Functional Foods and Nutritionology», candidate of Technical Sciences Volokolamskoe shosse, 11, Moscow, 125080, Russian Federation

Irina Chernukha

V.M. Gorbatov Federal Research Center for Food Systems of RAS

Email: imcher@inbox.ru
Principal researcher, Experimental clinic-laboratory of biologically active substances of animal origin; Doctor of Technical Sciences, Professor, Academician of RAS ul. Talalihina, 26, Moscow, 109316, Russian Federation

Lev Oganesyants

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»

Email: vniipbivp@fncps.ru
Scientific Director of Institute; Doctor of Technical Sciences, Professor, Academician of RAS ul. Rossolimo, 7, Moscow, 119021, Russian Federation

Andrey Durnev

V.V. Zakusov Research Institute of Pharmacology

Email: addurnev@mail.ru
expert scientific worker; Doctor of Medical Sciences, Professor, Corresponding Member of the RAS. Baltijskaya ul. 8, Moscow, 125315, Russian Federation

参考

  1. Guariguata L., Whiting D.R., Hambleton I., Beagley J., Linnenkamp U., Shaw J.E. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014; 103 (2): 137-49. https://doi.org/10.1016/j.diabres.2013.11.002.
  2. Forouhi N.G., Misra A., Mohan V., Taylor R., Yancy W. Dietary and nutritional approaches for prevention and management of type 2 diabetes. BMJ. 2018; 361: k2234. https://doi.org/10.1136/bmj.k2234.
  3. Еремина Н.В., Жанатаев А.К., Лисицын А.А., Дурнев А.Д. Генотоксические маркеры у больных сахарным диабетом (обзор литературы). Экологическая генетика. 2021; 19 (2): 143-68. https://doi.org/10/17816/ecogen65073.
  4. Дурнев А.Д., Жанатаев А.К., Еремина Н.В. Генетическая токсикология. М.: «Миттель-пресс», 2022.
  5. Aleisa A.M., Al-Rejaie S.S., Bakheet S.A., Al-Bekari A.M., Al-Shabanah O.A., Al-Majed A., Al-Yahya A.A., Qureshi S. Effect of metformin on clastogenic and biochemical changes induced by adriamycin in Swiss albino mice. Mutat Res. 2007; 634 (1-2): 93-100. https://doi.org/10.1016/j.mrgentox.2007.06.005.
  6. Attia S.M., Helal G.K., Alhaider A.A. Assessment of genomic instability in normal and diabetic rats treated with metformin. ChemBiol Interact. 2009; 180 (2): 296-304. https://doi.org/10.1016/j.cbi.2009.03.001
  7. Furman B.L. Streptozotocin-Induced Diabetic Models in Mice and Rats. Curr Protoc Pharmacol. 2015; 70: 5.47.1-5.47.20. https://doi.org/10.1002/0471141755.ph0547s70.
  8. Методические рекомендации МР 2.3.1.191504 «Рекомендуемые уровни потребления пищевых и биологически активных веществ» (утв. Федеральной службой по надзору в сфере защиты прав потребителей и благополучия человека 2 июля 2004 г.).
  9. Дурнев А.Д., Меркулов В.А., Жанатаев А.К., Никитина В.А., Воронина Е.С., Середенин С.Б. Методические рекомендации по оценке ДНК-повреждений методом щелочного гель-электрофореза отдельных клеток в фармакологических исследованиях. Руководство по проведению доклинических исследований лекарственных средств. Часть первая. - М.: Гриф и К, 2012.
  10. Жанатаев А.К., Анисина Е.А., Чайка З.В., Мирошкина И.А., Дурнев А.Д. Феномен атипичных ДНК-комет. Цитология. 2017; 59 (3): 163-8.
  11. Möller P., Loft S. Statistical analysis of comet assay results. Front Genet. 2014; 5: 292. https://doi.org/10.3389/fgene.2014.00292.
  12. Еремина Н.В., Жанатаев А.К., Дурнев А.Д. Индуцируемая клеточная гибель как возможный путь антимутагенного воздействия. Бюллетень экспериментальной биологии и медицины. 2021; 171 (1): 4-22. https://doi.org/10.47056/0365-9615-2021-171-1-4-22.
  13. Островская Р.У., Ягубова С.С., Жанатаев А.К., Анимина Е.А., Гудашева Т.А., Дурнев А.Д. Нейропротективный дилепт ноопепт предотвращает повреждения ДНК на модели преддиабета у мышей. Бюллетень экспериментальной биологии и медицины. 2019; 168 (8): 185-90.
  14. Maruthur N.M., Tseng E., Hutfless S., Wilson L.M., Suarez-Cuervo C., Berger Z., Chu Y., Iyoha E., Segal J.B., Bolen S. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Ann Intern Med. 2016; 164 (11): 740-51. https://doi.org/10.7326/M15-2650

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2. Fig. 1. The level of DNA damage in the organs of mice on day 10 (a) and day 21 (б) after administration of 200 mg/kg streptozocin; on days 14 (в) and 28 days (г) after a 5 days of daily administration of 40 mg/kg streptozotocin. * – p<0.01 compared with the control group «Кон» (Mann–Whitney U-test), «СД» – a group of animals with diabetes induced by streptozotocin

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3. Fig. 2. Effect of the aspartame+betaine (СД + АБ) combination and metformin (СД + М) on the DNA damage and atypical DNA comets in the diabetes mice organs (СД) induced by a single administration of 200 mg/kg streptozocin (a) or repeated administration of 40 mg/kg streptozocin (б). For %DNA in the tail: * – p<0.01 compared with the control group (Kon), # – p<0.01 compared with the DM group (Mann-Whitney U-test); for % of atypical DNA comets: * – p<0.01 compared to the control group (χ2 test)

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