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Open Access Journal of Pharmaceutical Research Research Article 28 min read

Contents of Nineteen Chemical Elements in Thyroid Benign Nodules and Tissue adjacent to Nodules investigated using X-Ray Fluorescence and Neutron Activation Analysis

Zaichick V*
* Corresponding author
ISSN: 2574-7797  10.23880/oajpr-16000260  Received: December 24, 2021  Published: February 15, 2022
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Keywords
Thyroid Thyroid Benign Nodules Chemical Elements X-Ray Fluorescence Neutron Activation Analysis
Abstract

Thyroid benign nodules (TBNs) are the most common diseases of this endocrine gland and are common worldwide. The etiology and pathogenesis of TBNs must be considered as multifactorial. The present study was performed to clarify the role of some chemical elements (ChEs) in the etiology of these thyroid disorders. Thyroid tissue levels of Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn were prospectively evaluated in nodular tissue and tissue adjacent to nodules of 79 patients with TBNs. Measurements were performed using X-ray fluorescence and instrumental neutron activation analysis. Results of the study were additionally compared with previously obtained data for the same ChEs in “normal” thyroid tissue. It was observed that mass fractions of Ag, Cl, Co, Cr, Cu, Fe, Hg, Mn, Na, and Sc contents in “nodular” tissue were higher, while Ca and I content was lower in comparison with contents of these ChEs in normal gland. Mass fractions of Ag, Cl, Hg, Na, and Rb in “adjacent” group of samples were approximately 31, 2.7, 32, 1.6, and 1.3 times higher, respectively, than in “normal” thyroid. Contents of Cr, Fe, Sc, and Se were lower, while mass fraction of Hg and I higher in “adjacent” group of samples in comparison with nodular tissue. At that, level of I in “adjacent” group of samples was over 2 times higher than in nodular tissue and almost equals the normal value. This study provides evidence on many ChEs level alteration in nodular and adjacent to nodule tissue and shows the necessity to continue ChEs research of TBNs. The little reduced level of I content in nodular tissue could possibly be explored for differential diagnosis of TBNs and thyroid cancer

Introduction

Thyroid benign nodules (TBNs) are universally encountered and frequently detected by palpation during a physical examination, or incidentally, during clinical imaging procedures. TBNs include non-neoplastic lesions, for example, colloid goiter and thyroiditis, as well as neoplastic lesions such as thyroid adenomas [1, 2, 3]. For over 20th century, there was the dominant opinion that TBNs is the simple consequence of iodine deficiency. However, it was found that TBNs is a frequent disease even in those countries and regions where the population is never exposed to iodine shortage [4]. Moreover, it was shown that iodine excess has severe consequences on human health and associated with the presence of TBNs [5, 6, 7, 8]. It was also demonstrated that besides the iodine deficiency and excess many other dietary, environmental, and occupational factors are associated with the TBNs incidence [9, 10, 11]. Among these factors a disturbance of evolutionary stable input of many chemical elements (ChEs) in human body after industrial revolution plays a significant role in etiology of TBNs [12].

Besides iodine, many other ChEs have also essential physiological functions [13]. Essential or toxic (goitrogenic, mutagenic, carcinogenic) properties of ChEs depend on tissue-specific need or tolerance, respectively [13]. Excessive accumulation or an imbalance of the ChEs may disturb the cell functions and may result in cellular proliferation, degeneration, death, benign or malignant transformation [13, 14, 15].

In our previous studies the complex of in vivo and in vitro nuclear analytical and related methods was developed and used for the investigation of iodine and other ChEs contents in the normal and pathological thyroid [16, 17, 18, 19, 20, 21, 22]. Iodine level in the normal thyroid was investigated in relation to age, gender and some non-thyroidal diseases [23, 24]. After that, variations of many ChEs content with age in the thyroid of males and females were studied and age- and gender-dependence of some ChEs was observed [25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41]. Furthermore, a significant difference between some TEs contents in colloid goiter, thyroiditis, and thyroid adenoma in comparison with normal thyroid was demonstrated [42, 43, 44, 45, 46].

To date, the etiology and pathogenesis of TBNs must be considered as multifactorial. The present study was performed to find out differences in ChEs contents between the group of nodular tissues and tissue adjacent to nodules, as well as to clarify the role of some ChEs in the etiology of TBNs. Having this in mind, the aim of this exploratory study was to examine differences in the content of silver (Ag), calcium (Ca), chlorine (Cl), cobalt (Co), chromium (Cr), cooper (Cu), iron (Fe), mercury (Hg), iodine (I), potassium (K), magnesium (Mg), manganese (Mn), sodium (Na), rubidium (Rb), ammonium (Sb), scandium (Sc), selenium (Se), strontium (Sr), and zinc (Zn) in nodular and adjacent to nodules tissues of thyroids with TBNs using a non-destructive energy-dispersive X-Ray fluorescent analysis (EDXRF) combined with instrumental neutron activation analysis with high resolution spectrometry of short- and long-lived radionuclides (INAA-SLR and INAA-LLR, respectively), and to compare the levels of these ChEs in two groups (nodular and adjacent to nodules tissues) of the cohort of TBNs samples. Moreover, for understanding a possible role of ChEs in etiology and pathogenesis of TBNs results of the study were compared with previously obtained data for the same ChEs in “normal” thyroid tissue [42, 43, 44, 45, 46].

Material and Methods

All 79 patients suffered from TBNs (46 patients with colloid goiter, mean age M±SD was 48±12 years, range 30-64; 19 patients with thyroid adenoma, mean age M±SD was 41±11 years, range 22-55; and 14 patients with thyroiditis, mean age M±SD was 39±9 years, range 34-50) were hospitalized in the Head and Neck Department of the Medical Radiological Research Centre (MRRC), Obninsk. The group of patients with thyroiditis included 8 persons with Hashimoto’s thyroiditis and 6 persons with Riedel’s Struma. Thick-needle puncture biopsy of suspicious nodules of the thyroid was performed for every patient, to permit morphological study of thyroid tissue at these sites and to estimate their ChEs contents. For all patients the diagnosis has been confirmed by clinical and morphological/histological results obtained during studies of biopsy and resected materials.

“Normal” thyroids for the control group samples were removed at necropsy from 105 deceased (mean age 44±21 years, range 2-87), who had died suddenly. The majority of deaths were due to trauma. A histological examination in the control group was used to control the age norm conformity, as well as to confirm the absence of micro-nodules and latent cancer.

All studies were approved by the Ethical Committees of MRRC. All the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments, or with comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

All tissue samples were divided into two portions using a titanium scalpel [47]. One was used for morphological study while the other was intended for ChEs analysis. After the samples intended for ChEs analysis were weighed, they were freeze-dried and homogenized [48].

To determine contents of the ChE by comparison with a known standard, biological synthetic standards (BSS) prepared from phenol-formaldehyde resins were used [49]. In addition to BSS, aliquots of commercial, chemically pure compounds were also used as standards. Ten sub-samples of certified reference material (CRM) of the International Atomic Energy Agency (IAEA) IAEA H-4 (animal muscle) and IAEA HH-1 (human hair) weighing about 100 mg were treated and analyzed in the same conditions as thyroid samples to estimate the precision and accuracy of results.

The content of Cu, Fe, Rb, Sr, and Zn were determined by EDXRF. Details of the relevant facility for this method, source with 109Cd radionuclide, methods of analysis and the results of quality control were presented in our earlier publications concerning the EDXRF of ChE contents in human thyroid and prostate tissue [25, 26, 50].

The content of Br, Ca, Cl, I, K, Mg, Mn, and Na were determined by INAA-SLR using a horizontal channel equipped with the pneumatic rabbit system of the WWR-c research nuclear reactor (Branch of Karpov Institute, Obninsk). Details of used neutron flux, nuclear reactions, radionuclides, gamma-energies, spectrometric unit, sample preparation and measurement were presented in our earlier publications concerning the INAA-SLR of ChE contents in human thyroid, prostate and scalp hair [27, 28, 51, 52, 53].

In a few days after non-destructive INAA-SLR all thyroid samples were repacked and used for INAA-LLR. A vertical channel of the WWR-c research nuclear reactor (Branch of Karpov Institute, Obninsk).was applied to determine the content of Ag, Co, Cr, Fe, Hg, Rb, Sb, Sc, Se, and Zn by INAA-LLR. Details of used neutron flux, nuclear reactions, radionuclides, gamma-energies, spectrometric unit, sample preparation and measurement were presented in our earlier publications concerning the INAA-LLR of ChE contents in human thyroid, scalp hair, and prostate [29, 30, 53, 54].

A dedicated computer program for INAA-SLR and INAA- LLR mode optimization was used [55]. All thyroid samples for ChEs analysis were prepared in duplicate and mean values of ChEs contents were used in final calculation. Mean values of ChE contents were used in final calculation for the Fe, Rb, and Zn mass fractions measured by two methods. Using Microsoft Office Excel software, a summary of the statistics, including, arithmetic mean, standard deviation, standard error of mean, minimum and maximum values, median, percentiles with 0.025 and 0.975 levels was calculated for ChEs contents in nodular and adjacent tissue of thyroids with TBNs. Data for “normal” thyroid were taken from our previous publications [42, 43, 44, 45, 46]. The difference in the results between three groups of samples (“normal”, “nodular”, and “adjacent”) was evaluated by the parametric Student’s t-test and non-parametric Wilcoxon-Mann-Whitney U-test.

Results

Table 1 presents certain statistical parameters (arithmetic mean, standard deviation, standard error of mean, minimal and maximal values, median, percentiles with 0.025 and 0.975 levels) of the Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn mass fraction in nodular and adjacent to nodules tissue of thyroid with TBN (“nodular” and “adjacent” group of thyroid tissue samples).

TissueElementMeanSDSEMMinMaxMedianP 0.025P 0.975
TBNAg0.4740.6620.130.0213.310.2820.05162.07
adjacent tissueCa1532170038041864669944426312
Cl9203603313842881237318161329422429
Co0.07280.09790.0170.00510.5940.05250.00860.219
Cr0.5750.6180.1080.0183.140.4010.05962.19
Cu10.27.943.620.48.353.6519.8
Fe2131402441.562017158.2557
Hg1.360.960.170.0144.681.210.2684.25
I21581436214343791219175275441
K679340448623406182555607350018077
Mg316275591598729215890
Mn1.771.660.360.15.831.10.15.67
Na10850554112094663313439642554823981
Rb10.54.20.74.1209.84.7419.4
Sb0.1310.1740.030.00760.7570.07590.02690.749
Sc0.00580.01470.0020.00020.06540.00020.00020.0468
Se1.950.870.150.6474.341.650.9063.66
Sr6.285.172.591.313.55.151.5412.9
Zn1211182034.266991.343401
TBNAg0.2260.2190.0310.0020.8740.1790.00220.808

nodular tissue M – arithmetic mean, SD – standard deviation, SEM – standard error of mean, Min – minimum value, Max –maximum value, P 0.025 – percentile with 0.025 level, P 0.975 – percentile with 0.975 level. Table 1: Some statistical parameters of Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn mass fraction (mg/ kg, dry mass basis) in nodular and adjacent to nodules tissue of thyroid with benign nodules (TBN).

The ratios of means and the comparison of mean values of Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn mass fractions in pairs of sample groups such Ca 1237 902 138 52 4333 1108 116 3536 Cl 8231 3702 772 1757 16786 8326 2543 15157 Co 0.0615 0.0332 0.0046 0.0083 0.159 0.0579 0.0152 0.141 Cr 0.966 0.844 0.121 0.075 3.65 0.673 0.109 2.76 Cu 10.2 9.2 1.7 2.9 35.2 6 3.04 34.9 Fe 387 475 56 52,3 2563 188 60 1739 Hg 0.924 0.649 0.088 0.0817 3.01 0.856 0.104 2.12 I 991 906 105 29 3906 690 84.7 3632 K 6191 2360 352 797 12222 6185 1438 10297 Mg 331 180 26 13 844 311 15 745 Mn 1.8 1.38 0.21 0.1 5.54 1.45 0.367 5.48 Na 10207 3786 558 2319 22381 9802 3689 16969 Rb 9.16 4.21 0.5 1 20.3 8.6 2.48 17.9 Sb 0.137 0.116 0.016 0.0024 0.466 0.101 0.0112 0.423 Sc 0.0144 0.0217 0.003 0.0002 0.091 0.0058 0.0002 0.0878 Se 2.75 2.13 0.29 0.72 12.6 2.31 1.05 10 Sr 4.48 6.84 0.88 0.42 32 1.9 0.769 27.5 Zn 115.3 49.6 5.9 47 270 105 48.8 248 as “normal” and “nodular”, “normal” and “adjacent”, and also “adjacent” and “nodular” are presented in Table 2, 3, and 4, respectively.

ElementThyroid tissueRatio
NTTBN nodularStudent’s t-test p≤U-test pTBN nodular/NT
Ag0.0151±0.00160.226±0.0310.000000008≤0.0115
Ca1711±1091237±1380.0082≤0.010.72
Cl3400±1748231±7720.0000025≤0.012.42
Co0.0399±0.00300.0615±0.00460.00016≤0.011.54
Cr0.539±0.0320.966±0.1210.0012≤0.011.79
Cu4.23±0.1810.2±1.70.0018≤0.012.41
Fe223±10387±560.0055≤0.011.74
Hg0.0421±0.00410.924±0.0880.00000000001≤0.0121.9
I1841±107991±1050.000000058≤0.010.54
K6071±3066191±3520.797>0.051.02
Mg285±17331±260.140>0.051.16
Mn1.35±0.071.80±0.210.048≤0.011.33
Na6702±17810207±5580.00000018≤0.011.52
Rb8.16±0.499.16±0.500.153>0.051.12
Sb0.111±0.0080.137±0.0160.143>0.051.23
Sc0.0046±0.00080.0144±0.00300.0054≤0.013.13
Se2.32±0.142.75±0.290.174>0.051.19
Sr4.55±0.374.48±0.880.948>0.050.98
Zn105.1±4.3115.3±5.90.163>0.051.1

Table 2: Differences between mean values (M±SEM) of Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn

M – Arithmetic mean, SEM – standard error of mean, Sstatistically significant values is in bold. Table 2: Differences between mean values (M±SEM) of Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn mass fraction (mg/kg, dry mass basis) in normal thyroid (NT) and thyroid benign nodules (TBN) (nodular tissue).

ElementThyroid tissueRatio
NTTBN adjacentStudent’s t-test p≤U-test pTBN adjacent/NT
Ag0.0151±0.00160.474±0.1300.0016≤0.0131.4
Ca1711±1091532±3800.654>0.050.9
Cl3400±1749203±13840.00056≤0.012.71
Co0.0399±0.00300.0728±0.01700.061≤0.051.82
Cr0.539±0.0320.575±0.1080.750>0.051.07
Cu4.23±0.1810.2±4.00.230>0.052.41
Fe223±10213±240.691>0.050.96
Hg0.0421±0.00411.36±0.170.000000005≤0.0132.3
I1841±1072158±2140.188>0.051.17
K6071±3066793±8620.437>0.051.12
Mg285±17316±590.610>0.051.11
Mn1.35±0.071.77±0.360.271>0.051.31
Na6702±17810850±12090.0028≤0.011.62
Rb8.16±0.4910.5±0.70.013≤0.011.29
Sb0.111±0.0080.131±0.0300.512>0.051.18
Sc0.0046±0.00080.0058±0.00200.647>0.051.26
Se2.32±0.141.95±0.150.072>0.050.84
Sr4.55±0.376.28±2.590.554>0.051.38
Zn105.1±4.3121±200.438>0.051.15

Table 3: Differences between mean values (M±SEM) of Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn

M – Arithmetic mean, SEM – standard error of mean, Sstatistically significant values is in bold. Table 3: Differences between mean values (M±SEM) of Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn mass fraction (mg/kg, dry mass basis) in normal thyroid (NT) and thyroid benign nodules (TBN) (adjacent tissue).

ElementThyroid tissueRatio
TBN adjacentTBN nodularStudent’s t-test, p≤U-test, pNodular/adjacent
Ag0.474±0.1300.226±0.0310.074>0.050.48
Ca1532±3801237±1380.473>0.050.81
Cl9203±13848231±7720.545>0.050.89
Co0.0728±0.01700.0615±0.00460.522>0.050.84
Cr0.575±0.1080.966±0.1210.018≤0.011.68
Cu10.2±4.010.2±1.70.999>0.051
Fe213±24387±560.0055≤0.011.82
Hg1.36±0.170.924±0.0880.024≤0.010.68
I2158±214991±1056.7E-06≤0.010.46
K6793±8626191±3520.523>0.050.91
Mg316±59331±260.82>0.051.05
Mn1.77±0.361.80±0.210.95>0.051.02
Na10850±120910207±5580.633>0.050.94
Rb10.5±0.79.16±0.500.154>0.050.87
Sb0.131±0.0300.137±0.0160.873>0.051.05
Sc0.0058±0.00200.0144±0.00300.039≤0.012.48
Se1.95±0.152.75±0.290.015≤0.011.41
Sr6.28±2.594.48±0.880.551>0.050.71
Zn121±20115.3±5.90.778>0.050.95

Table 4: Differences between mean values (M±SEM) of Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn

M – Arithmetic mean, SEM – standard error of mean, Sstatistically significant values is in bold. Table 4: Differences between mean values (M±SEM) of Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn mass fraction (mg/kg, dry mass basis) in nodular and adjacent tissue of thyroid benign nodules (TBN)

Discussion

As was shown before good agreement of the Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn contents in CRM IAEA H-4 and IAEA HH-1 (human hair) samples determined by EDXRF, INAA-SLR, and INAA-LLR with the certified data of these CRMs indicates acceptable accuracy of the results obtained in the study of thyroid tissue samples presented in Tables 1–4 [25, 26, 27, 28, 29, 30, 50, 51, 52, 53, 54].

The Ag, Cl, Co, Cr, Cu, Fe, Hg, Mn, Na, and Sc contents in “nodular” tissue were higher, while Ca and I content was lower in comparison with contents of these ChEs in normal gland (Table 2). Significant differences between ChEs contents of “normal” thyroid and ChEs contents of thyroid tissue adjacent to nodules were found for Ag, Cl, Hg, Na, and Rb. Mass fractions of Ag, Cl, Hg, Na, and Rb in “adjacent” group of samples were approximately 31, 2.7, 32, 1.6, and 1.3 times, respectively, higher than in “normal” thyroid (Table 3). In a general sense Ag, Ca, Cl, Co, Cu, K, Mg, Mn, Na, Rb, Sb, Sr, and Zn contents found in the “nodular” and “adjacent” groups of thyroid tissue samples were very similar (Table 4). However, mass fraction of Cr, Fe, Sc, and Se were lower, while mass fraction of Hg and I higher in “adjacent” group of samples (Table 4). At that, level of I in “adjacent” group of samples was over 2 times higher than in nodular tissue (Table 4) and almost equals the normal value (Table 3).

Characteristically, elevated or reduced levels of ChEs observed in thyroid nodules are discussed in terms of their potential role in the initiation and promotion of these thyroid lesions. In other words, using the low or high levels of the ChEs in affected thyroid tissues researchers try to determine the role of the deficiency or excess of each ChEs in the etiology and pathogenesis of thyroid diseases. In our opinion, abnormal levels of many ChEs in TBNs could be and cause, and also effect of thyroid tissue transformation. From the results of such kind studies, it is not always possible to decide whether the measured decrease or increase in ChEs level in pathologically altered tissue is the reason for alterations or vice versa. According to our opinion, investigation of ChEs contents in thyroid tissue adjacent to nodules and comparison obtained results with ChEs levels typical of “normal” thyroid gland may give additional useful information on the topic because this data show conditions of tissue in which TBNs were originated and developed. For example, results of this study demonsrate that contents Ag, Cl, Hg, Na, and Rb in thyroid tissue in which TBNs were originated and developed were significantly higher the levels which are “normal” for thyroid gland, while I content almost equals of normal level.

Silver

Ag is a TE with no recognized trace metal value in the human body [56]. Food is the major intake source of Ag and this metal is authorised as a food additive (E174) in the EU [57]. Another source of Ag is contact with skin and mucosal surfaces because Ag is widely used in different applications (e.g., jewelry, wound dressings, or eye drops) [58]. Ag in metal form and inorganic Ag compounds ionize in the presence of water, body fluids or tissue exudates. The silver ion Ag+ is biologically active and readily interacts with proteins, amino acid residues, free anions and receptors on mammalian and eukaryotic cell membranes [59]. Besides such the adverse effects of chronic exposure to Ag as a permanent bluish- gray discoloration of the skin (argyria) or eyes (argyrosis), exposure to soluble Ag compounds may produce other toxic effects, including liver and kidney damage, irritation of the eyes, skin, respiratory, and intestinal tract, and changes in blood cells [60]. Experimental studies shown that Ag nanoparticles may affect thyroid hormone metabolism [61]. More detailed knowledge of the Ag toxicity can lead to a better understanding of the impact on human health, including thyroid function.

Chlorine and Sodium

Cl and Na are ubiquitous, extracellular electrolytes essential to more than one metabolic pathway. In the body, Cl and Na mostly present as sodium chloride. Therefore, as usual, there is a correlation between Na and Cl contents in tissues and fluids of human body. Because Cl is halogen like I, in the thyroid gland the biological behavior of chloride has to be similar to the biological behavior of iodide. The main source of natural Cl for human body is salt in food and chlorinated drinking water. Environment (air, water and food) polluted by artificial nonorganic Cl-contained compounds, for example such as sodium chlorate (NaClO3), and organic Cl-contained compounds, for example such as polychlorinated biphenyls (PCBs) and dioxin, is other source. There is a clear association between using chlorinated drinking water, levels NaClO3, PCBs and dioxin in environment and thyroid disorders, including cancer [62, 63, 64, 65, 66]. Thus, on the one hand, the accumulated data suggest that Cl level in thyroid tissue might be responsible for TBNs development. However, on the other hand, it is well known that Cl and Na mass fractions in human tissue samples depend mainly on the extracellular water volume [67]. Nodular and adjacent to nodules thyroid tissues can be more vascularized and can contain more relative volume of colloid that normal thyroid. Because blood and colloid are extracellular liquids, it is possible to speculate that it could be the reason for elevated levels of Cl and Na in TBNs and adjacent tissue. If that is the case the equilibrium between Cl and Na increases has to be, however, in comparison with “normal” thyroid the change of Cl level in TBNs and adjacent tissue is significantly higher than change of Na level. Thus, it is possible to assume that an excessive accumulation of Cl in thyroid tissue is involved in TBNs etiology. Overall, the elevated levels of Cl in thyroid tissue could possibly be explored as risk factor of TBNs.

Mercury

In the general population, potential sources of Hg exposure include the inhalation of this metal vapor in the air, ingestion of contaminated foods and drinking water, and exposure to dental amalgam through dental care [68]. Hg is one of the most dangerous environmental pollutants [69].

The growing use of this metal in diverse areas of industry has resulted in a significant increase of environment contamination and episodes of human intoxication. Many experimental and occupational studies of Hg in different chemical states shown significant alterations in thyroid hormones metabolism and thyroid gland parenchyma [70, 71]. Moreover, Hg was classified as certain or probable carcinogen by the International Agency for Research on Cancer [72]. For example, in Hg polluted area thyroid cancer incidence was almost 2 times higher than in adjacent control areas [73].

Rubidium

There is very little information about Rb effects on thyroid function. Rb as a monovalent cation Rb+ is transfered through membrane by the Na+K+-ATPase pump like K+ and concentrated in the intracellular space of cells. Thus, Rb seems to be more intensivly concentrated in the intracellular space of cells. The sourse of Rb elevated level in TBNs tissue may be Rb environment overload. The excessive Rb intake may result a replacement of medium potassium by Rb, which effects on iodide transport and iodoaminoacid synthesis by thyroid [74]. The sourse of Rb increase in TBNs tissue may be not only the excessive intake of this TE in organism from the environment, but also changed Na+K+ -ATPase or H+K+ - ATPase pump membrane transport systems for monovalent cations, which can be stimulated by endocrin system, including thyroid hormones [75]. It was found also that Rb has some function in immune responce and that elevated concentration of Rb could modulate proliferative responses of the cell, as was shown for bone marrow leukocytes [76, 77]. These data partially clarify the possible role of Rb in etiology and pathogenesis of TBNs.

Iodine

To date, it was well established that I deficiency or excess has severe consequences on human health and associated with the presence of TBNs [5, 6, 7, 8, 78]. However, in present study neither reduced nor elevated levels of I in thyroid tissue adjacent to nodules in comparison with “normal” thyroid tissue were not found.

Compared to other soft tissues, the human thyroid gland has higher levels of I, because this element plays an important role in its normal functions, through the production of thyroid hormones (thyroxin and triiodothyronine) which are essential for cellular oxidation, growth, reproduction, and the activity of the central and autonomic nervous system. As was shown in present study, benign nodular transformation is probably accompanied by a partial loss of tissue-specific functional features, which leads to a modest reduction in I content associated with functional characteristics of the human thyroid tissue. Little reduced level of I content in nodular tissue could possibly be explored for differential diagnosis of TBNs and thyroid cancer, because, as was found in our ealier studies, thyroid malignant trasformation is accompanied by a drastically loss of I accumulation [18, 79, 80, 81].

Limitations

This study has several limitations. Firstly, analytical techniques employed in this study measure only nineteen ChE (Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn) mass fractions. Future studies should be directed toward using other analytical methods which will extend the list of ChEs investigated in “normal” thyroid and in pathologically altered tissue. Secondly, the sample size of TBNs group was relatively small and prevented investigations of ChEs contents in this group using differentials like gender, histological types of TBNs, nodules functional activity, stage of disease, and dietary habits of patients with TBNs. Lastly, generalization of our results may be limited to Russian population. Despite these limitations, this study provides evidence on many ChEs level alteration in nodular and adjacent to nodule tissue and shows the necessity to continue ChEs research of TBNs.

Conclusion

In this work, ChEs analysis was carried out in the tissue samples of TBNs using a combination of three non- destructive methods: EDXRF, INAA-SLR and INAA-LLR. It was shown that this combination is an adequate analytical tool for the non-destructive determination of Ag, Ca, Cl, Co, Cr, Cu, Fe, Hg, I, K, Mg, Mn, Na, Rb, Sb, Sc, Se, Sr, and Zn content in the tissue samples of human thyroid in norm and pathology, including needle-biopsy specimens. It was observed that mass fractions of Ag, Cl, Co, Cr, Cu, Fe, Hg, Mn, Na, and Sc contents in “nodular” tissue were higher, while Ca and I content was lower in comparison with contents of these ChEs in normal gland. Mass fractions of Ag, Cl, Hg, Na, and Rb in “adjacent” group of samples were approximately 31, 2.7, 32, 1.6, and 1.3 times higher, respectively, than in “normal” thyroid. Contents of Ag, Ca, Cl, Co, Cu, K, Mg, Mn, Na, Rb, Sb, Sr, and Zn found in the “nodular” and “adjacent” groups of thyroid tissue samples were very similar, however, mass fraction of Cr, Fe, Sc, and Se were lower, while mass fraction of Hg and I higher in “adjacent” group of samples. At that, level of I in “adjacent” group of samples was over 2 times higher than in nodular tissue and almost equals the normal value.

Conflicts of Interest

The author has not declared any conflict of interests.

Acknowledgements

The author is extremely grateful to Profs. B.M. Vtyurin and V.S. Medvedev, Medical Radiological Research Center, Obninsk, as well as to Dr. Yu. Choporov, former Head of the Forensic Medicine Department of City Hospital, Obninsk, for supplying thyroid samples.

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@article{zaichick2022,
  title   = {Contents of Nineteen Chemical Elements in Thyroid Benign Nodules and Tissue adjacent to Nodules investigated using X-Ray Fluorescence and Neutron Activation Analysis},
  author  = {Zaichick V},
  journal = {Open Access Journal of Pharmaceutical Research},
  year    = {2022},
  volume  = {6},
  number  = {1},
  doi     = {10.23880/oajpr-16000260}
}
Zaichick V (2022). Contents of Nineteen Chemical Elements in Thyroid Benign Nodules and Tissue adjacent to Nodules investigated using X-Ray Fluorescence and Neutron Activation Analysis. Open Access Journal of Pharmaceutical Research, 6(1). https://doi.org/10.23880/oajpr-16000260
TY  - JOUR
TI  - Contents of Nineteen Chemical Elements in Thyroid Benign Nodules and Tissue adjacent to Nodules investigated using X-Ray Fluorescence and Neutron Activation Analysis
AU  - Zaichick V
JO  - Open Access Journal of Pharmaceutical Research
PY  - 2022
VL  - 6
IS  - 1
DO  - 10.23880/oajpr-16000260
ER  -