Резюме
Єрьоменко Р.Ф., Малоштан Л.М., Щербак О.А. Вивчення впливу коректора білкового обміну екстракту з трави люцерни посівної на рівень тиреоїдних гормонів.
Встановлено, що в умовах гіпертиреозу, спричиненого левотироксином, у щурів відбувається підвищення рівня тиреоїдних гормонів тироксину (Т4) і трийодтироніну (Т3). Препарат порівняння калію оротат в дозі 180 мг/кг достовірно відносно групи КП знижував в крові рівень Т4 - на 28%, а Т3 - на 18%. Потенційно новий коректор білкового обміну ЕТЛП в дозі 25 мг/кг достовірно відносно групи КП сприяв зниженню в крові щурів з гіпертиреозом рівня Т4 на 26%, а Т3 - на 31%, що обумовлено вмістом в ньому крім білків і амінокислот, які прямо попереджали порушення білкового обміну, ще й поліфенолів (дубильні речовини) і органічні кислоти (кавова, галова, ферулова), що забезпечують антитиреоїдний (антигормональний) ефект. Враховуючи здатність тиреоїдних гормонів регулювати інтенсивність білкового обміну та отримані результати, можна зробити висновок про те, що ЕТЛП в дозі 25 мг/кг краще препарату порівняння калію оротат в дозі 180 мг/кг здатний попереджати розвиток гіпертиреозу у щурів за рахунок впливу на тиреоїдні гормони Т4 та Т3.
Ключові слова: білковий обмін, екстракт з трави люцерни посівної, корекція білкового обміну, тироксин (Т4), трийодтиронін (Т3), гіпертиреоз.
Резюме
Еременко Р.Ф., Малоштан Л.Н., Щербак А.А. Изучение влияния корректора белкового обмена экстракта из травы люцерны посевной на уровень тиреоидных гормонов.
Установлено, что в условиях гипертиреоза, вызванного левотироксином, у крыс происходит повышение уровня тиреоидных гормонов тироксина (Т4) и трийодтиронина (Т3). Препарат сравнения калия оротат в дозе 180 мг/кг достоверно относительно группы КП снижал в крови уровень Т4 – на 28%, а Т3 – на 18%.Потенциально новый корректор белкового обмена ЭТЛП  в дозе 25 мг/кг достоверно относительно  группы КП способствовал снижению уровня в крови крыс с гипертиреозом Т4 на 26%, а Т3 – на 31%, что обусловлено содержанием в нем кроме белков и аминокислот, которые прямо предупреждали нарушения белкового обмена, еще и полифенолы (дубильне вещества) и органические кислоты (кофейная, галловая, феруловая), обеспечивающие антитиреоидный (антигормональный) эффект. Учитывая способность тиреоидных  гормонов регулировать интенсивность белкового обмена и полученные результаты, можно сделать вывод о том, что ЭТЛП в дозе 25 мг/кг лучше препарата сравнения калия оротат в дозе 180 мг/кг способен предупреждать развитие гипертиреоза у крыс за счет влияния на тиреоидиные гормоны Т4 та Т3.
Ключевые слова: белковый обмен, экстракт из травы люцерны посевной, коррекция белкового обмена, тироксин (Т4), трийодтиронин (Т3), гипертиреоз.
Summary
Yerоmenko R.F., Maloshtan L.N., Shcherbak Ye.A. Study of the extract Medicago sativa sowing grass protein metabolism corrector influencing the level of thyroid hormones.
It has been determined that in conditions of hyperthyroidism caused by levothyroxine an increase in the level of thyroid hormones thyroxine (T4) and triiodothyronine (T3) can be observed in animals’ blood. Comparative drug potassium orotate in doses of 180 mg/kg has reduced the levels of T4 and T3 in the blood of animals from CP group by 28% and 18% correspondingly. A potentially new EGMS protein metabolism corrector in doses of 25 mg/kg has contributed to relatively lower levels of T4 and T3 in the blood of rats suffering from hyperthyroidism (CP group) by 26% and 31% correspondingly, which is due to the proteins and amino acids that directly prevent disorders of protein metabolism and to polyphenols (tannins) and organic acids (caffeic, gallic, ferulic) which provide antithyroid (antihormonal) effect. Given the ability of thyroid hormone to regulate the intensity of protein metabolism and observing the results obtained, we can conclude that EGMS in doses of 25 mg/kg can better prevent the development of hyperthyroidism in rats than comparative drug potassium orotate in doses of 180 mg/kg due to the influence of thymidine hormones T4 and T3.
Key words: protein metabolism, extract Medicago sativa sowing grass, correction of protein metabolism, thyroxine (T4), triiodothyronine (T3), hyperthyroidism.

УДК 615.32:577.122:591.147:615.076.9:59

Національний фармацевтичний університет (Харків)

Национальный фармацевтический университет (Харьков) 61002, г. Харьков, ул. Пушкинская, 53
National University of Pharmacy (Kharkov) Ukraine, 61002, Kharkov, 53, str. Pushkinska

fuatovna@rambler.ru

Introduction. Thymidine hormones thyroxine (T₄) and triiodothyronine (T₃) that stimulate metabolism in the body are involved in the regulation of protein metabolism: triiodothyronine that is formed from thyroxine adds to the receptors in the cell nucleus and influences the gene causing transcription and translation, thus stimulating protein synthesis in all body cells [8]. Also Thymidine hormones affect the exchange of Na⁺ and K⁺, the size of mitochondria: at high levels of thyroid hormones their activity increases greatly and mitochondria increase in size, increase the activity of many enzymes leading to an increase in the rate of energy metabolism. This causes a direct correlation between the intensity of metabolism, including protein metabolism, and the concentration of thyroid hormones in     blood [7, 8].

So the above mentioned shows the leading role of thyroid hormones thyroxine (T₄) and triiodothyronine (T₃) in maintenance of protein homeostasis and proves the necessity of studying the affect on its concentration in the blood of a new protein metabolism corrector Medicago sativa sowing grass extract’s protein metabolism corrector (EGMS) (Medicago sativa) which belongs to legumes (Fabaceae) [6, 9, 10, 11] serving as a source of protein, amino acids, including essential ones, enzymes that split proteins and facilitate their assimilation, other biologically active substances with antioxidant, membrane-regulating, protecting, anti-inflammatory and other properties that may indirectly control hormone levels and protein metabolism [2, 3, 5].

Connection of the work with academic programs, plans, topics.

The dissertation is performed within the research program of the National Pharmaceutical University "Pharmacological studies of biologically active substances and drugs of synthetic and natural origin, their use in medical practice» (state registration № 0103U000478).

Purpose of the work is examining and comparing the impact of EGMS and potassium orotate on the level of thyroid hormones thyroxine (T₄) and triiodothyronine (T₃) in the rats’ blood serum in conditions of hyperthyroidism caused by levothyroxine [1].

Materials and methods of research

The experiment was carried out on 32 white rats weighing 180-200 g. in compliance with NPhU’s Commission of Bioethics’s "General ethical principals of carrying out experiments with animal " (Kyiv, 2001) that correspond to "The European Convention for the protection of vertebrate animals used for experimental and scientific purposes"(Strasbourg, 1986) [4]. The animals were divided into the following: 1 group - intact control (IC), 2 group - control pathology (CP), 3 group – research group being injected EGMS in doses of 25 mg/kg, 4 group – research group being injected potassium orotate in doses of 180 mg/kg. After that the animals were injected the above mentioned medicine in the stated doses, CP group were injected with dissolvent for 10 days before and 20 days when injecting levothyroxine. Hyperthyroidism was caused by intragastric administration of levothyroxine (1 mg/kg) to CP and the two research groups during 20 days. On the 21-th day the animals were weighed and taken out of the experiment by means of barbamyl anesthesia, blood was collected to determine the level of thyroid hormones T₃ and T₄ by immunosorbent analysis [1, 4].

The experimental data were treated by methods of variation statistics using a standard statistical software package «Statistica 6.0». To draw statistical conclusions parametric methods (method by Nyuman-Keyls) has been applied. The level of significance taken by comparing statistical samples equals to p <0.05. The results are given in Table 1.

Obtained results and discussions

According to the results of the study intragastric administration of levothyroxine in doses of 1mg/kg leads to hyperthyroidism, that can be proved by such signs of thyrotoxicosis present as aggressiveness, polyphagia, weight loss, breath shortness, tachycardia at the end of experiment, and which can be seen on intact control group having an increase in T₄ (33%) and T₃ (39%) levels in animals’ blood (see Table 1).

Table 1

The affect of EGMS and comparative drug on the level of thyroid hormones T₃ and T₄ by hyperthyroidism caused by levothyroxine

Notes:

* - deviation rate is relative to intact control group, p £0,05;

** - deviation rate is relative to the control of disease, p £ 0,05.

Therapeutic and prophylactic administration of EGMS in doses of 25mg/kg and comparative drug potassium orotate in doses of 180 mg/kg prevented from the development of hyperthyroidism in animals that becomes evident from the reduction of such signs of thyrotoxicosis, as polyphagia, weight loss and tachycardia, and the impact on the level of thyroid hormones (see Table 1). Thus EGMS in doses of 25 mg/kg used in CP group contributed to lowing of T₄ to T₃ levels in the blood of rats suffering from hyperthyroidism by 26% and 31% correspondingly. Potassium orotate in doses of 180 mg/kg also used in CP group has significantly reduced the T₄ and T₃ levels by 28% and 18% correspondingly. Such different influence of drugs on the level of thyroid hormones is due to the fact that EGMS contains not only proteins and amino acids that directly prevent disorders of protein metabolism, but also polyphenols (tannins) and organic acids (caffeic, gallic, ferulic) which according to bibliography [1] provide antithyroid (antihormonal) effect. Taking into account the ability of thyroid hormone to regulate the intensity of protein metabolism and in accordance with the results obtained, we can conclude that EGMS in doses of 25 mg/kg is a more effective means in preventing the development of hyperthyroidism in rats than comparative drug potassium orotate in doses of 180 mg/kg due to the influence of thymidine hormones T₄ and T₃.

Conclusions

1. It has been found that by hyperthyroidism caused by levothyroxine  an increase in the level of thyroid hormones thyroxine (T₄) and triiodothyronine (T₃) can be observed. Comparative drug potassium orotate in doses of 180 mg/kg has reduced the levels of T₄ and T₃ in the blood of animals from CP group by 28% and 18% correspondingly.
2. A potentially new EGMS protein metabolism corrector in doses of 25 mg/kg has contributed to relatively lower levels of T₄ and T₃ in the blood of rats suffering from hyperthyroidism (CP group) by 26% and 31% correspondingly, which is due to the proteins and amino acids that directly prevent disorders of protein metabolism and to polyphenols (tannins) and organic acids (caffeic, gallic, ferulic) which provide antithyroid (antihormonal) effect.
3. Given the ability of thyroid hormone to regulate the intensity of protein metabolism and observing the results obtained, we can conclude that EGMS in doses of 25 mg/kg is better in preventing the development of hyperthyroidism in rats than comparative drug potassium orotate in doses of 180 mg/kg due to the influence of thymidine hormones T₄ and T₃, which is the reason for the further research in order to examine the therapeutic efficiency of the new protein metabolism corrector.

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