QUERCETIN AND DIHYDROQUERCETIN POLYPHENOLS REDUCE IODINE DEFICIENCY IN CASE OF HYPOTHYROIDISM

ABSTRACT

Hypothyroidism leads to a decrease in metabolism which caused by a lack of iodine in the consumed food. This leads to an insufficient supply of oxygen to tissues which income various pathological changes [5, p. 943]. Any diseases in the body outcome with increasing free radicals [2, p. 673]. Determination of the correction mechanisms of physiological and biochemical disorders of biologically active substances at the cellular and mitochondrial levels is becoming relevant in a biomedical science. It has been shown that dihydroquercetin and quercetin flavonoids reduce the thyroid deficiency with the antiradical effect which the influence of the active form of oxygen.

АННОТАЦИЯ

Гипотиреоз приводит к снижению обмена веществ, что обусловлено недостатком йода в потребляемой пище. Это приводит к недостаточному снабжению кислородом тканей, в которых происходят различные патологические изменения [5, c. 943]. Любые заболевания в организме исходят из увеличения количества свободных радикалов [2, c. 673]. Определение механизмов коррекции физиологических и биохимических нарушений биологически активных веществ на клеточном и митохондриальном уровнях становится актуальным с точки биомедицинской науки. Показано, что дигидрокверцетин и флавоноиды кверцетина уменьшают недостаточность щитовидной железы с антирадикальным эффектом, обусловленным влиянием активной формы кислорода.

Keywords: quercetin, dihydroquercetin, mercazalin.

Ключевые слова: кверцетин, дигидрокверцетин, мерказалин.

Introduction. Deficiency of thyroid hormones in the body leads to a decrease in metabolism. This leads to an insufficient supply of oxygen to tissues or a destruction of its usage, which leads to various pathological changes. In the body in case of hypothyroidism the changes are shown in peripheral tissues. The general metabolic effects of thyroid hormones include a relative acceleration of basic metabolism, which includes an increase in the rate of catabolic and anabolic reactions. This leads to an increase in energy expenditure, oxygen consumption, respiration rate and heat production. The hormone thyroxine can alter the process of oxidative stress. Dysfunction of the mitochondrial respiratory chain due to hypothyroidism can lead to accelerated production of free radicals [5, p. 943].

Materials and methods. In the experiments, white laboratory male rats weighing 100–120 g were used. The animals were divided into experimental and control groups. The experimental group animals were induced with mercazalin orally at a dose of 10 mg / kg for 14 days, and the control group animals were induced with 1.0 ml of saline [6, c. 27]. Blood was taken from the tails of control and experimental animals on the 15th day of the experiment.

Thyroid hormones, triiodothyronine (T₄) and thyroxine (T₃) act at the cellular level by binding to a set of specialized receptors associated with genomic and non-genomic signaling pathways [4, p. 1132]. In hypothyroidism mainly in the peripheral tissues ditructions are observed in the body. Due to their strong antioxidant properties, the quercetin and dihydroquercetin flavonoids reduce mitochondrial dysfunction caused by hypothyroidism and, as can be seen, improve the amount of hormones in the blood by combining the resulting free radicals.

In an intact body, the amount of thyroxine decreased by 29.0% in case of hypothyroidism from the level of 5.38±0.05 ng/ml, and with inducing dihydroquercetin the rate of this hormone increased to 83%. Quercetin is more effective than dihydroquercetin, which increased the amount of this hormone to 93.4%. The amount of triiodothyronine in a healthy body was 1.74 ± 0.04 ng / ml, which declined to 71.3% with a decrease in thyroid function and this quantity increased to 87.4% with inducing of dihydroquercetin. When corrected with quercetin, the amount of this hormone in the blood increased to 83.3%. (tab.1)

Table-1.

In all cases: p<0,01**, p<0,001***, p<0,05*,

The level of free thyroxine in a healthy organism was 1.68 ± 0.05 pg/ml and this number decreased by 25.6% after hypothyroidism. When corrected with dihydroquercetin, this amount increased to 90.4%, which is close to the share of a healthy organism. In rats treated with quercetin, this figure is grew to 94.0%. The level of free triiodothyronine was 4.73 ± 0.06 pg/ml, which was relatively low in experimental hypothyroidism (54.3%). This number increased to 89.0% with inducing dihydroquercetin. The biological activity of quercetin was higher than dihydroquercetin, which increased the amount of free triiodothyronine in the blood to 94.5% [3, p. 66].

Thyroid cells are formed by the follicule wall which the epithelium of the thyroid gland. In the follicle cavity there is a colloid containing thyroid hormones. Follicular cells are various size depending on their activity. When follicles are at rest (inactive), follicular cells are smooth [2, p. 674]. When the follicles are very active, the follicular cells turn into a simple column with a few collisions. During normal activity, in the normal state of the follicles, the cells become simple cuboid, and the cavity is filled with an average amount of colloid [1, p. 187 ].

During the histological experiments, morphological changes in the structure of the thyroid follicles were revealed.

Figure 1.The morphological changes of the thyroid gland of rats

In intact animals, the follicles of the thyroid gland have a round or oval shape (Fig. A), in the intrafollicular cavity there is a colloid, thyroglobulin. Thyrocytes are cubic in shape. There is little difference between the follicles. For normal thyrocyte cytoplasm is characterized by oxyphilic staining. In the cavity of the follicles is a colloid having, like the cytoplasm of thyrocytes, pale oxyphilic staining with rare vacuoles resorption. Between the follicles are found interfollicular cells. In the center of the gland was occupied by the follicles of medium size, and large on the periphery. In all areas of thyroid follicles in intact animals had clear contours and distinct cavity and uniform staining of the colloid. In the pooled subgroup of animals without differentiation on metabolic rate during reproduction of experimental hypothyroidism was observed destructive processes in the thyroid gland. In regional areas were defined collapsed thyroid follicles of small size. It was noted the heterogeneity of the tissue structure of the thyroid gland. Some follicles were lined by flattened epithelium, containing colloid is pale and marked desquamation of the epithelium into the cavity of the follicle. The Central most area of the thyroid gland, devoid of follicles, was homogeneous, represented by the epithelium, most likely resulting from the destroyed follicles. In the center of the gland revealed a considerable portion of the tissue detritus is the one with deposits of hemosiderin [1, p. 187].  The second day of taking mercazolil: in the rats their daytime activity decreased and  sleeping hours increased. From the 3rd day of the experiment, signs of aggressive behavior were noted; the large follicles filled with colloid in small follicles colloid is absent. On day 9, two rats developed motor paralysis. In most of the thyroid follicles, the colloid is absent; the follicles are small, edematous interlobular tissue. The thyroid follicles of varying sizes filled with colloid, stroma permeated by lymphocytes, expanded interlobular layer. On the 14th day of body weight at a dose of 10 mg / 100 g, functional depletion of the thyroid gland was noted (Fig. B). Deformed follicles with signs of destruction of thyrocytes were found. Thyrocytes with colloid-free intrafollicular cavities were empty.  lymphoplasmacytic diffuse infiltration of stroma of thyroid gland with atrophy of follicles, a single follicle in a state of hypertrophy and filled with colloid, in other parts of the proliferation and hyperplasia of glandular tissue. The lobules of the thyroid gland, surrounded by the follicles of different shapes and sizes. Most follicles atrophic, small colloid absent, interlobular spaces are dilated. There is hyperemia of the vessels.

Figure 2. The morphological changes of the thyroid gland of rats

The daily activity of rats increased when taking flavonoids. The appetite of the rats improved, their movements accelerated. The wall of thyroid follicles is regenerated, the shape of thyrocytes is clearly visible, inside the follicles are filled with colloid. [C,D] The thyroid nucleus also enlarged, and the activity of most cells was restored. There was an acceleration of blood circulation in the vessels of the cells of the glandular tissue, along with these changes, the production of the hormones thyroxine and triiodothyronine also accelerated. Both quercetin and dihydroquercetin showed tissue regeneration, normalized body metabolism and energy metabolism.

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