Screening study of the psychotropic activity of neuropeptide compounds in conditions of mercazolyl hypothyroidism

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Abstract

Introduction. To date, there has been an increase in thyroid diseases mediated by a violation of regulatory mechanisms on the part of the central structures of the hypothalamic-pituitary-thyroid system. Numerous scientific studies have revealed that the emerging thyroid imbalance in thyroid diseases causes the development of metabolic syndrome, disorders of the cardiovascular system, as well as neuropsychic changes, which are often the first clinical manifestations of thyroid pathology. The current direction today is the study and development of means of correction of possible neuropsychic disorders. Of interest are the compounds of the peptide structure, on the basis of which effective drugs with a wide variety of pharmacological properties are being synthesized today. It has been proven that peptide compounds have neurotropic, psychotropic, anxiolytic, and other pharmacological effects due to their effect on the functional activity of neurotransmitter systems.

The aim of the study was a screening study of the psychotropic activity of peptide compounds in conditions of hypofunction of the thyroid gland.

Material and methods. The study was conducted on male rats divided into groups: I-th – control animals; II-th – individuals with induced hypothyroidism; III, IV, V, VI, VII and VIII-th – animals treated with hypothyroidism, respectively, Thr-Lys-Pro-Arg-Pro-Gly-Pro, ACTH(4-7)-Pro-Gly-Pro, ACTH(6-9)-Pro-Gly-Pro, Pro-Gly-Pro, Pro-Gly-Pro-Leu, Arg-Pro-Gly-Pro, Pro-Gly-Pro-Val and Met-Thr-Lys-Pro-Arg-Pro-Gly-Pro doses 87; 87; 89; 33; 44; 42; 42; 88 mcg/kg/day, which were 1/10 of the molecular weight of the studied substances. The psychotropic activity of the studied peptides was studied using the Open Field test.

Results. It was found that in the conditions of experimental hypothyroidism, there is an inhibition of motor and exploratory activity against the background of an increase in anxiety levels (duration of freezing, grooming reactions and the number of defecations). The studied peptide compounds had a corrective effect to varying degrees on the psychoemotional state of laboratory animals in conditions of hypofunction of the thyroid gland.

Conclusions. The results of a screening study in a number of regulatory peptides indicate that the compounds ACTH(4-7)-Pro-Gly-Pro and ACTH(6-9)-Pro-Gly-Pro have the most pronounced psychotropic activity in relation to behavioral indicators in the Open Field test under conditions of experimental hypothyroidism.

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About the authors

М. U. Sergalieva

Astrakhan State Medical University of the Ministry of Health of Russia

Author for correspondence.
Email: charlina_astr@mail.ru
ORCID iD: 0000-0002-9630-2913

Ph.D. (Biol.), Associate Professor of the Department of Pharmacognosy, Pharmaceutical Technology and Biotechnology

Russian Federation, 121 Bakinskaya St., Astrakhan, 414000

А. А. Tsibizova

Astrakhan State Medical University of the Ministry of Health of Russia

Email: sasha3633@yandex.ru
ORCID iD: 0000-0002-9994-4751

Ph.D. (Pharm.), Associate Professor of the Department of Pharmacognosy, Pharmaceutical Technology and Biotechnology

Russian Federation, 121 Bakinskaya St., Astrakhan, 414000

М. А. Samotrueva

Astrakhan State Medical University of the Ministry of Health of Russia

Email: ms1506@mail.ru
ORCID iD: 0000-0001-5336-4455

Dr.Sc. (Med.), Professor, Head of the Department of Pharmacognosy, Pharmaceutical Technology and Biotechnology

Russian Federation, 121 Bakinskaya St., Astrakhan, 414000

References

  1. Стяжкина С.Н., Порываева Е.Л., Валинуров А.А. Актуальные вопросы диагностики и лечения заболеваний щитовидной железы. Медико-фармацевтический журнал «Пульс». 2017; 19(8): 144–146. [Styazhkina S.N., Poryvaeva E.L., Valinurov A.A. Topical issues of diagnosis and treatment of thyroid diseases. Mediko-farmatsevticheskii zhurnal «Pul's». 2017; 19(8): 144–146. (In Russ.)].
  2. Медяник М.И., Похлебкина А.А., Мильнер Е.Б. Ожирение и щитовидная железа. Некоторые механизмы взаимосвязи. Университетский терапевтический вестник. 2021; 3(2): 13–24. [Medyanik M.I., Pokhlebkina A.A., Mil'ner E.B. Obesity and thyroid gland. Some mechanisms of interconnection. Universitetskii terapevticheskii vestnik. 2021;3(2):13-24. (In Russ.)].
  3. Беккер Р.А., Быков Ю.В. О роли нейроэндокринных нарушений в патогенезе когнитивной дисфункции при депрессивных состояниях (обзор литературы с комментариями). ConsiliumMedicum. 2016; 4: 57–61. [Bekker R.A., Bykov Yu.V. On the role of neuroendocrine disorders in the pathogenesis of cognitive dysfunction in depressive states (literature review with comments). ConsiliumMedicum. 2016; 4: 57–61. (In Russ.)].
  4. Дамулин И.В., Оразмурадов Г.О. Неврологические нарушения при гипотиреозе. Журнал неврологии и психиатрии им. С.С. Корсакова. 2011;111(3):82-86. [Damulin I.V., Orazmuradov G.O. Neurological disorders in hypothyroi-dism. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2011; 111(3): 82–86. (In Russ.)].
  5. Эркенова Л.Д. Морфологические изменения головного мозга при гипотиреозе. Кубанский научный медицинский вестник. 2012; 1: 197–199. [Erkenova L.D. Morphological changes of the brain in hypothyroidism. Kubanskii nauchnyi meditsinskii vestnik. 2012; 1: 197–199. (In Russ.)].
  6. Додонова С.А., Белых А.Е., Бобынцев И.И. Регуляторные пептиды семейства меланокортинов: биосинтез, рецепция, биологические эффекты. Человек и его здоровье. 2018; 1: 1–10. [Dodonova S.A., Belykh A.E., Bobyntsev I.I. Regulatory peptides of the melanocortin family: biosynthesis, reception, biological effects. Chelovek i ego zdorov'e. 2018;1:1-10. (In Russ.)].
  7. Glazova N.Yu., Manchenko D.M., Volodina M.A. et al. Semax, synthetic ACTH(4–10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats. Neuropeptides. 2021; 86: 102114. doi: 10.1016/j.npep.2020.102114.
  8. Жуйкова С.Е. Физиологические и клинические эффекты синтетического аналога АКТГ4–10 семакса и его механизмы действия. Интегративная физиология. 2022; 3(2): 204–220. doi: 10.33910/2687-1270-2022-3-2-204-220. [Zhuikova S.E. Physiological and clinical effects of the synthetic analogue of ACTH4–10 semax and its mechanisms of action. Integrativnaya fiziologiya. 2022; 3(2): 204–220. (In Russ.)]. doi: 10.33910/2687-1270-2022-3-2-204-220.
  9. Vyunova T.V., Andreeva L.A., Shevchenko K.V. et al. Synthetic corticotropins and the GABA-receptor system: Direct and delayed effects. Chem Biol Drug Des. 2023; 101(6): 1393–1405. doi: 10.1111/cbdd.14221.
  10. Sharonova I.N., Bukanova Y.V., Myasoedov N.F. et al. Modulation of GABA- and Glycine-Activated Ionic Currents with Semax in Isolated Cerebral Neurons. Bull Exp Biol Med. 2018; 164: 612–616. doi: 10.1007/s10517-018-4043-8.
  11. Giuliani D., Ottani A., Neri L. et al. Multiple beneficial effects of melanocortin MC4 receptor agonists in experimental neurodegenerative disorders: Therapeutic perspectives. Progress in Neurobiology. 2017; 148: 40–56. doi: 10.1016/j.pneurobio.2016.11.004.

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2. Fig. 1. The effect of regulatory peptides on motor activity indicators in the Open field test under conditions of experimental hypothyroidism: *;** – p≤0,05; p≤0,01 relative to control; #; ## – p≤0,05; p≤0,01 relative to hypothyroidism

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3. Fig. 2. The effect of regulatory peptides on anxiety indicators in the Open field test under conditions of experimental hypothyroidism: * – p≤0,05 relative to control; #; ## – p≤0,05; p≤0,01 relative to hypothyroidism

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4. Fig. 3. The effect of regulatory peptides on specific «mink» activity in the Open field test under conditions of experimental hypothyroidism: ** – p≤0,01 relative to control; #; ## – p≤0,05; p≤0,01 relative to hypothyroidism

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