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Influence of exogenous melatonin on the oxidative status and the state of peroxidation of proteins in a rat model of alimentary obesity

https://doi.org/10.14341/omet9561

Abstract

Not only lipids, but also proteins are exposed to the action of reactive oxygen species (ROS). Oxidative modification of proteins (PBS) leads to a change in their native conformation with the formation of large aggregates, it causes inactivation of enzymes, disrupts the metabolism and functioning of cells. In addition, there is a growing interest in studying the hormone of the pineal gland called melatonin, as well as its synthetic analogues as the leading protection factors in the oxidative stress conditioned by disturbed physiological rhythms, including obesity. The peculiarities of protein peroxidation in the case of alimentary obesity, as well as the conditions affecting to this process, in contrast to lipid peroxidation (LPO), have not been studied sufficiently, that has determined the purpose of this study.


Aim. To evaluate the effect of exogenous melatonin on the oxidative status and features of PBS in rats with alimentary obesity.


Methods. The study was conducted on 27 white Wistar male rats with body weight 160–180 grams. Animals were divided into 3 series of 9 rats in each: 1 series – intact animals; 2 series – animals with alimentary obesity, followed by the introduction of 0,9% sodium chloride solution in a volume of 2 ml for 12 days; 3 series – animals with alimentary obesity followed by melatonin administration at a dose of 2 mg / kg rats for 12 days. Alimentary obesity was reproduced by feeding animals with high-calorie carbohydrate-fatty food, consisting of a laboratory feed "Assortment Agro" (42.5%), butter (25%) and sweet condensed milk (32.5%) for seven weeks. The maximum physical working capacity and resistance of rats to severe hypobaric hypoxia were determined. PBS was determined by the method of R. Levine in the modification of E.E. Dubinina. In addition, the lipid peroxidation marker – TBA-reactive products (malonic dialdehyde MDA) was determined.


Results. It has been established that the PBS in alimentary obesity is not specific, it is reflected in the increase in the areas of absorption of light from both the visible and ultraviolet of aldehyde and ketondinitrophenylhydrazones. In parallel with this, there was a marked increase in the concentration of TBA-reactive products in the blood serum in this pathology, as well as a significant decrease in the resistance of rats to hypobaric hypoxic hypoxia and maximum physical activity. The daily administration of a 2 mg/kg melatonin suspension to rats with alimentary obesity for 12 days leads to a significant decrease in the concentration of TBA-reactive products, however, the PBS is not significantly affected.


Conclusion. Alimentary obesity in rats, simulated by the maintenance of animals on a high-calorie carbohydrate-fat diet, leads to an increase in the proportion of visceral fat in the body, an increase in the activity of PBS in the form of an increase in the level of carbonyl derivatives, a significant increase in the concentration of MDA, and a significant decrease in the stability of rats to hypobaric hypoxic hypoxia and maximum physical activity. When a melatonin suspension was administered at a dose of 2 mg/kg for 12 days, a stable high level of carbonyl derivatives was observed, in comparison with the intact series, which was explained by the need to use a greater concentration of the drug to increase its exposure time, which requires further study.

About the Authors

Victor V. Davydov

Ryazan State Medical University


Russian Federation

ScD, Professor



Dmitry V. Medvedev

Ryazan State Medical University


Russian Federation

assistant of the department



Dmitry R. Shodiev

Ryazan State Medical University


Russian Federation

student



Marina S. Nekrasova

Ryazan State Medical University


Russian Federation

student



References

1. Бутрова С.А., Плохая А.А. Ожирение и сахарный диабет: общность этиологии и профилактики // Сахарный диабет. – 2005. – № 3. – С.45–50. [Butrova S.A., Plokhaya A.A. Ozhirenie i sakharnyi diabet: obshchnost' etiologii i profilaktiki // Sakharnyi diabet. 2005;(3):45-50. (In Russ).]

2. Бородин Е.А., Бородина Г.П., Доровский В.А. и др. Перекисное окисление липидов в мембранах эритроцитов и микросом печени и антиокислительная система тканей крыс при длительном действии холода // Биологические мебраны. – 1992. – Т.9. – №6. – С.622 – 627. [Borodin E.A., Borodina G.P., Dorovskii V.A. i dr. Perekisnoe okislenie lipidov v membranakh eritrotsitov i mikrosom pecheni i antiokislitel'naya sistema tkanei krys pri dlitel'nom deistvii kholoda // Biologicheskie mebrany. 1992;9(6): 622 – 627. (In Russ).]

3. Chakravarti B., Chakravarti D.N. Oxidative Modification of Proteins: Age-Related Changes // Gerontology. 2007;53:128–139. doi:10.1159/000097865

4. Nystrom T. Role of oxidative carboxylation in protein quality control and senescence // The EMBO Journal. 2005;24(7):1311 – 1317. doi:10.1038/sj.emboj.7600599

5. Davies K. J. A., Delsignore M. E., Lin S. W. Protein Damage and Degradation by Oxygen Radicals // Journal of Biological Chemistry. 1987; 262(20): 9908 – 9913.

6. Дубинина Е.Е. Продукты метаболизма кислорода в функциональной активности клеток // СПб: Медицинская пресса, 2006. – C. 400. [Dubinina E.E. Produkty metabolizma kisloroda v funktsional'noi aktivnosti kletok // St. Petersburg: Meditsinskaya pressa; 2006. p. 400. (In Russ).]

7. Ernst A, Stolzing A, Sandig G, Grune T. Protein oxidation and the degradation of oxidized proteins in the rat oligodendrocyte cell line OLN 93-antioxidative effect of the intracellular spin trapping agent PBN. Mol Brain Res. 2004. doi: 10.1016/j.molbrainres.2003.12.005

8. Caraceni P., De Maria N., Ryu H.S. Et al. Colantoni A., Roberts L., Maidt M.L., Pye Q., Bernardi M., Van Thiel D.H., Floyd R.A. Proteins but not nucleic acids are molecular targets for the free radical attack during reoxygenation of rat hepatocytes //Free Radic. Biol. Med. 1997;23(2):339 – 344. doi:10.1016/S0891-5849(96)00571-0

9. Halliwell B. Reactive Oxygen Species and the Central Nervous System. J Neurochem. 1992. doi: 10.1111/j.1471-4159.1992.tb10990.x

10. Agarwal S., Sohal R.S. Differential oxidative damage to mitochondrial proteins during aging // Mech. Ageing. Dev. 1995; 85(1):55 – 63. doi:10.1016/0047-6374(95)01655-4

11. Forster M.J., Dubey A., Dawson K.M., Stutts W.A., Lal H., Sohal R.S. Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain // Proc. Natl.Acad. Sci. 1996;93(10):4765 – 4769. doi:10.1073/pnas.93.10.476.5

12. Арапова А.И., Фомина М.А. Изучение влияния L-карнитина на изменение активности катепсинов B, L, H и окислительной модификации белков в мышечных органах крыс // Российский медико-биологический вестник имени академика И.П. Павлова. − 2016 г. – Т. 24. − №2. – C.13−20. [Arapova A.I., Fomina M.A. Izuchenie vliyaniya L-karnitina na izmenenie aktivnosti katepsinov B, L, H i okislitel'noj modifikacii belkov v myshechnyh organah krys // Rossijskij mediko-biologicheskij vestnik imeni akademika I.P. Pavlova. 2016; 24(2):13−20 (In Russ).]

13. Александрова Л.Н., Анисимов В.Н., Арушанян Э.Б. и др. Мелатонин: перспективы применения в клинике // под ред. Рапопорт С.И. – М.: ИМА-ПРЕСС, 2012. – С.176. [Aleksandrova L.N., Anisimov V.N., Arushanyan E.B. I dr. Melatonin: perspektivy primeneniya v klinike // in. Rapoport S.I. Moscow: IMA-PRESS; 2012. p.176. (In Russ).]

14. Reiter R.J., Acuna-Castroviejo D.,Tan D.X. Free radical mediated molecular damage mechanisms for the Protective Actions of Melatonin in the Central Nervous System // An. N.Y. Acad. Sci. 2001;939:200–215. doi:10.1111/j.1749-6632.2001.tb03627.x

15. C. Rodriguez, J.C. Mayo, R.M. Sainz. Regulation of antioxidant enzymes: a significant role for melatonin // Jour. Pin. Res. 2004;36(1):1–9. doi:10.1046/j.1600-079x.2003.00092.x

16. Никоноров А.А., Тиньков А.А., Железнов Л.М. И др. Методический подход к изучению ожирения в эксперименте // Оренбург: ОАО «ИПК «Южный Урал», 2013. – C. 240. [Nikonorov A.A., Tin'kov A.A., Zheleznov L.M. At al. Metodicheskii podkhod k izucheniyu ozhireniya v eksperimente // Orenburg: OAO «IPK «Yuzhnyi Ural»; 2013. p.240 (In Russ).]

17. Дубинина Е.Е., Бурмистров С.О., Ходов Д.А. И др. Окислительная модификация белков сыворотки крови человека, метод её определения // Вопросы медицинской химии. – 1995. –Т.41. – № 1. – С. 24–26. [Dubinina E.E., Burmistrov S.O., Khodov D.A. At al. Oxidative modification of human serum proteins. A method of determining it // Vopr. Med. Khim. 1995;41(1):24 – 26. (In Russ).]

18. Конюхова С.Г., Маркин С.Г., Конюхова А.А., и др. Перекисное окисление липидов и методы определения продуктов липопероксидации в биологических средах // Лабораторное дело. – 1989. – № 9. – С. 40–46. [Konyukhova S.G., Markin S.G., Konyukhova A.A. At al. Perekisnoe okislenie lipidov i metody opredeleniya produktov lipoperoksidatsii v biologicheskikh sredakh // Laboratornoe delo. 1989;(9):40 – 46. (In Russ).]

19. Ильичева А.С., Фомина М.А., Медведев Д.В. Характеристика продуктов окислительного повреждения белков миокарда на фоне гипергомоцистеинемии // Наука молодых. – 2014. –№4. – С.37 – 43. [Il'icheva A.S., Fomina M.A., Medvedev D.V. Characteristic products of oxidative damage of proteins in heart muscle with hyperhomocysteinemia // ERUDICIO JUVENIUM. 2014;(4):37 – 43. (In Russ).]

20. Давыдов В.В., Медведев Д.В., Шодиев Д.Р., Некрасова М.С. Влияние нарушения светового режима на липидный обмен и функциональные показатели у интактных крыс и животных с алиментарным ожирением // Наука молодых. – 2017. – T.5. – №2. – С.175 – 184.[Davydov V.V., Medvedev D.V., Shodiev D.R., Nekrasova M.S. Effect of light regimes violations on lipid metabolism in infact rats and animals with alimentary obesity // ERUDICIO JUVENIUM. 2017;5(2):175–184. (In Russ).] doi: 10.23888/HMJ20172175-184

21. Alexander J.K., Turell D.J., Drew M.J. Mechanisms of dyspnea in obesity // Cardiovasc. Res. Cent. Bull.1963;16:27 – 32.

22. Gulcin, I.; Beydemir, S.; Hisar, O.; Koksal, E.; Reiter, R.J. Melatonin administration increases antioxidant enzymes activities and reduces lipid peroxidation in the rainbow trout (Oncorhynchus mykiss, Walbaum) erythrocytes // Turk. J. Vet. Anim. Sci., 2009, 33(3):241-245.

23. Фомина М.А., Абаленихина Ю.В. Способ комплексной оценки содержания продуктов окислительной модификации белков в тканях и биологических жидкостях: методические рекомендации; ГБОУ ВПО РязГМУ Минздрава. – Рязань: РИО РязГМУ, 2014. – C.60. [FominaM.A., Abalenikhina Yu.V. Sposob kompleksnoi otsenki soderzhaniya produktov okislitel'noi modifikatsii belkov v tkanyakh i biologicheskikh zhidkostyakh: metodicheskie rekomendatsii; GBOU VPO RyazGMU Minzdrava. Ryazan': RIO RyazGMU; 2014; p.60. (In Russ).]

24. Baraibar M.A., Ladouce R., Friguet B. Proteomic quantification and identification of carbonylated proteins upon oxidative stress and during cellular aging // Journal of Proteomics. 2013;92:67–70. doi:10.1016/j.jprot.2013.05.008

25. Vasil'ev Y. V. et al. Protein modifications by electrophilic lipoxidation products: Adduct formation, chemical strategies and tandem mass spectrometry for their detection and identification // Mass Spectrometry Reviews. 2013;33(3):157 – 182. doi: 10.1002/mas.21389

26. Albarran M.T., Lopez-Burillo S, Pablos M.I. et al. Endogenous rhythms of melatonin, total antioxidant status and superoxide dismutase activity in several tissues of chick and their inhibition by light // Journal of Pineal Research. 2001;30(4):227−233. doi:10.1034/j.1600-079x.2001.300406.x

27. Dun-Xian Tan, Russel J. Reiter et al. Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines // Journal of Pineal Research. 2009;47(2):109 – 126. doi:10.1111/j.1600-079x.2009.00701.x

28. Carmen Rodriguez, Juan C. Mayo et al. Regulation of antioxidant enzymes: a significant role for melatonin // Journal of Pineal Research. 2004; 36:1–9. doi:10.1046/j.1600-079X.2003.00092.x

29. Bahr I., Muhlbauer E., Schulte H. et al. Melatonin stimulates glucagon secretion in vitro and in vivo // Journal of Pineal Research 2011;50:336 − 344. doi: 10.1111/j.1600-079X.2010.00848.x

30. Peschke E, Mühlbauer E. New evidence for a role of melatonin in glucose regulation. Best Pract Res Clin Endocrinol Metab. 2010. doi: 10.1016/j.beem.2010.09.001

31. Darul K, Kruczyńska H. Effect of melatonin on biochemical variables of the blood in dairy cows. Acta Vet Hung. 2004;52(3):361-367. doi: 10.1556/AVet.52.2004.3.11

32. Cagnacci A, Arangino S, Renzi A, et al. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol (Oxf). 2001. doi: 10.1046/j.1365-2265.2001.01232.x


Supplementary files

1. Fig. 1. Dynamics of changes in body weight in rats 1-3 series
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2. Fig. 2. The amount of fat in rats of three series
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3. Fig. 3. Dynamics of changes in the resistance of rats of all series to hypobaric hypoxic hypoxia
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4. Fig. 4. Dynamics of change in the duration of the swimming test of rats of all series
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5. Fig. 5. Changes in the concentration of TBA-reactive products in the serum of rats 1-3 series
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6. Fig. 6. The total number of carbonyl derivatives of proteins
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7. Fig. 7. The share of the total number of ADNPG and KDNFG- relative to total carbonyl protein derivatives
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For citations:


Davydov V.V., Medvedev D.V., Shodiev D.R., Nekrasova M.S. Influence of exogenous melatonin on the oxidative status and the state of peroxidation of proteins in a rat model of alimentary obesity. Obesity and metabolism. 2018;15(4):15-21. (In Russ.) https://doi.org/10.14341/omet9561

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