Browsing by Author "Manojlović, Dragan (16744014700)"

Modest progress has been made in understanding the role of trace elements as endocrine disruptors. The aim of this study was to examine whether there is a change in the content of trace elements in thyroid disease, as well as whether the ratio of elements could be considered a blood marker for thyroid disease. In addition, this study examined the influence of biological and clinical/pathological parameters on the elemental profile. Blood samples from patients diagnosed with multinodular goiter (MNG), thyroid adenoma (TA), and thyroid cancer (TC) were examined and compared with control samples using chemometric analysis. The concentrations of essential (Mn, Co, Cu, Zn, Se) and toxic elements (Ni, As, Cd, Pb, U) were determined by ICP-MS. This study showed for the first time that the content of Mn, Co, Ni, Cu, Zn, Se, and Pb in pathological blood samples was significantly lower compared to the control, while opposite results were obtained for As, Cd, and U. Based on the classification model, the most important trace metals for discrimination of MNG and TC from the control group (CG) were Co and Zn, while Co, Zn, and Mn influenced the distinction of CG from TA. Moreover, it was found that Cu/Zn and U/Se ratios had significantly increased values in pathological blood samples leading to the possibility of establishing new circulating screening markers. These findings can represent significant translational information since these diseases are widespread and the diagnostic procedure is still difficult in many cases. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.

Modest progress has been made in understanding the role of trace elements as endocrine disruptors. The aim of this study was to examine whether there is a change in the content of trace elements in thyroid disease, as well as whether the ratio of elements could be considered a blood marker for thyroid disease. In addition, this study examined the influence of biological and clinical/pathological parameters on the elemental profile. Blood samples from patients diagnosed with multinodular goiter (MNG), thyroid adenoma (TA), and thyroid cancer (TC) were examined and compared with control samples using chemometric analysis. The concentrations of essential (Mn, Co, Cu, Zn, Se) and toxic elements (Ni, As, Cd, Pb, U) were determined by ICP-MS. This study showed for the first time that the content of Mn, Co, Ni, Cu, Zn, Se, and Pb in pathological blood samples was significantly lower compared to the control, while opposite results were obtained for As, Cd, and U. Based on the classification model, the most important trace metals for discrimination of MNG and TC from the control group (CG) were Co and Zn, while Co, Zn, and Mn influenced the distinction of CG from TA. Moreover, it was found that Cu/Zn and U/Se ratios had significantly increased values in pathological blood samples leading to the possibility of establishing new circulating screening markers. These findings can represent significant translational information since these diseases are widespread and the diagnostic procedure is still difficult in many cases. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.

Pheochromocytoma (PCC) is an unusual benign adrenal tumor with an unexamined status of the elements. This study delivers the first insight into the levels of microelements (Mn, Co, Cu, Zn, As, Se, Th), toxic elements (Cd, Pb, U), and macroelements (Na, K, Mg, Ca) in both adrenal tissue and whole blood samples collected from PCC patients. The results were strengthened by comparing recorded findings with the patients’ healthy adrenal tissue (HAT) and with whole blood samples from the healthy individuals. PCCs had significantly higher levels of Zn, Se, Na, K, and Mg and lower levels of Mn, Co, Pb, and As than that of HATs. Compared to healthy blood samples, the patients’ blood exhibited considerably higher levels of Na, K, and Ca but significantly lower levels of Mn, Cu, Zn, Se, and Mg. Females had significantly higher levels of essential Se and toxic Pb and Cd in their PCC tissue samples compared to males. PCC tissue levels of Mn and Cu were significantly elevated in smokers over levels in nonsmokers and in PCC patients with tumor sizes below 5 cm compared to PCC diameters above 5 cm. The data presented in this study provide a new insight into the pathophysiology of PCC. Thus, recorded elements should be considered as initiators/modifiers of PCC and potential inductors of malignant transformation. The findings of this research deepen scientific understanding of this rare adrenal disease, which, in turn, could highlight the pathogenesis of PCC. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Pheochromocytoma (PCC) is an unusual benign adrenal tumor with an unexamined status of the elements. This study delivers the first insight into the levels of microelements (Mn, Co, Cu, Zn, As, Se, Th), toxic elements (Cd, Pb, U), and macroelements (Na, K, Mg, Ca) in both adrenal tissue and whole blood samples collected from PCC patients. The results were strengthened by comparing recorded findings with the patients’ healthy adrenal tissue (HAT) and with whole blood samples from the healthy individuals. PCCs had significantly higher levels of Zn, Se, Na, K, and Mg and lower levels of Mn, Co, Pb, and As than that of HATs. Compared to healthy blood samples, the patients’ blood exhibited considerably higher levels of Na, K, and Ca but significantly lower levels of Mn, Cu, Zn, Se, and Mg. Females had significantly higher levels of essential Se and toxic Pb and Cd in their PCC tissue samples compared to males. PCC tissue levels of Mn and Cu were significantly elevated in smokers over levels in nonsmokers and in PCC patients with tumor sizes below 5 cm compared to PCC diameters above 5 cm. The data presented in this study provide a new insight into the pathophysiology of PCC. Thus, recorded elements should be considered as initiators/modifiers of PCC and potential inductors of malignant transformation. The findings of this research deepen scientific understanding of this rare adrenal disease, which, in turn, could highlight the pathogenesis of PCC. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Due to the recognized harmful effects of some trace elements on fetal development after long-term exposures, it is first important to address their basic/physiological levels before monitoring toxicological effects and clinical outcomes on prenatal and postnatal health. This research aimed to define, for the first time, reference values for multiple (ultra) trace elements in umbilical cord blood (UCB) plasma samples of a notable number of healthy pregnant women (n = 125). All samples were collected during 2020–2021 and all participants were from Belgrade and two regions (Šumadija and Podunavlje). Following trace elements were enrolled in this study: essential (Mn, Co, Cu, Zn, Se, Mo), toxic (Be, Al, Ni, As, Rb, Sr, Ag, Cd, Sb, Ba, Tl, Pb, Th, U), rare earth (La, Ce, Pr, Nd, Sm, Eu, Gd, Dy, Ho, Er, Tm), and noble metals (Ru, Rh, Pd, Re, Ir, Os, Pt). UCB plasma samples were diluted with suitable solvents and analyzed by inductively coupled plasma-mass spectrometry. The analytical technique used was validated by the standard addition method and using certified reference materials. Zn was found in the highest amount and Tm in the least amount. Be, Co, Ag, Sb, La, and Ce exhibited statistically significant differences in the four age groups (20 to 41 years), whereas Ag and Ce showed a tendency to increase with age. Furthermore, our participants had notably higher As, Ni, and Co, levels and lower Zn levels compared to other populations. This is the first study that, in addition to analyzing essential and toxic trace elements, also provided an analysis of noble and rare earth elements in UCB plasma samples. Presented results can be used as a starting point or database for further studies, in terms of predicting the pregnancy outcome and postnatal development. © 2021, The Author(s), under exclusive licence to Springer Nature B.V.

Due to the recognized harmful effects of some trace elements on fetal development after long-term exposures, it is first important to address their basic/physiological levels before monitoring toxicological effects and clinical outcomes on prenatal and postnatal health. This research aimed to define, for the first time, reference values for multiple (ultra) trace elements in umbilical cord blood (UCB) plasma samples of a notable number of healthy pregnant women (n = 125). All samples were collected during 2020–2021 and all participants were from Belgrade and two regions (Šumadija and Podunavlje). Following trace elements were enrolled in this study: essential (Mn, Co, Cu, Zn, Se, Mo), toxic (Be, Al, Ni, As, Rb, Sr, Ag, Cd, Sb, Ba, Tl, Pb, Th, U), rare earth (La, Ce, Pr, Nd, Sm, Eu, Gd, Dy, Ho, Er, Tm), and noble metals (Ru, Rh, Pd, Re, Ir, Os, Pt). UCB plasma samples were diluted with suitable solvents and analyzed by inductively coupled plasma-mass spectrometry. The analytical technique used was validated by the standard addition method and using certified reference materials. Zn was found in the highest amount and Tm in the least amount. Be, Co, Ag, Sb, La, and Ce exhibited statistically significant differences in the four age groups (20 to 41 years), whereas Ag and Ce showed a tendency to increase with age. Furthermore, our participants had notably higher As, Ni, and Co, levels and lower Zn levels compared to other populations. This is the first study that, in addition to analyzing essential and toxic trace elements, also provided an analysis of noble and rare earth elements in UCB plasma samples. Presented results can be used as a starting point or database for further studies, in terms of predicting the pregnancy outcome and postnatal development. © 2021, The Author(s), under exclusive licence to Springer Nature B.V.

Exposure to certain metals has been recognized as a risk factor for numerous complications in vulnerable population groups, particularly pregnant women. This investigation evaluated the levels of essential (Cr, Mn, Co, Cu, Zn, Se, Mo) and nonessential trace metals with recognized toxicity (Be, Al, Ti, V, Ni, Ga, As, Rb, Sr, Cd, Sb, Ba, Tl, Hg, Pb, Bi, Th, U), together with rare earth elements (Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Yb, Lu), and noble metals (Ru, Rh, Pd, Re, Os, Ir, Pt, Au, Ag) in the placental tissues of healthy pregnant women (n = 105). The selection of participants was undertaken with special reference to specific confounding factors that could influence the trace element profiles. Among trace elements, Zn was the most abundant and Lu was the least abundant. Cd and Os placental levels show a tendency to increase with women's age. Compared with literature data, high levels of Ni were found. This is the first study that provides the composition levels of essential and toxic trace elements, rare earth elements, and noble metals in human placental tissues. Also, for the first time, normal (reference) ranges for 50 (ultra)trace elements in placental tissues are proposed. Reference ranges are especially important in biomonitoring studies, which nowadays give increasing importance to the analysis of solid tissues instead of body fluids. Overall, the information provided in this study can serve as a starting point for further clinical trials and/or prediction of potential risks to pregnancy. © 2021 Elsevier Ltd

Exposure to certain metals has been recognized as a risk factor for numerous complications in vulnerable population groups, particularly pregnant women. This investigation evaluated the levels of essential (Cr, Mn, Co, Cu, Zn, Se, Mo) and nonessential trace metals with recognized toxicity (Be, Al, Ti, V, Ni, Ga, As, Rb, Sr, Cd, Sb, Ba, Tl, Hg, Pb, Bi, Th, U), together with rare earth elements (Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Yb, Lu), and noble metals (Ru, Rh, Pd, Re, Os, Ir, Pt, Au, Ag) in the placental tissues of healthy pregnant women (n = 105). The selection of participants was undertaken with special reference to specific confounding factors that could influence the trace element profiles. Among trace elements, Zn was the most abundant and Lu was the least abundant. Cd and Os placental levels show a tendency to increase with women's age. Compared with literature data, high levels of Ni were found. This is the first study that provides the composition levels of essential and toxic trace elements, rare earth elements, and noble metals in human placental tissues. Also, for the first time, normal (reference) ranges for 50 (ultra)trace elements in placental tissues are proposed. Reference ranges are especially important in biomonitoring studies, which nowadays give increasing importance to the analysis of solid tissues instead of body fluids. Overall, the information provided in this study can serve as a starting point for further clinical trials and/or prediction of potential risks to pregnancy. © 2021 Elsevier Ltd

Breast cancer (BC) is a multifactorial disease with unresolved etiology. Environmental pollutants, primarily trace metals, play a pivotal role in the pathophysiological cascade of malignant tumors, including BC. In this up-to-date review, we comprehensively and critically examined the relationship between cadmium (Cd) and BC. For this purpose, peer-reviewed studies from relevant databases (PubMed, SCOPUS, and Cochrane Library) over the last 40 years were retrieved and analyzed. We found that in vitro and in vivo studies strongly support the view that Cd has harmful effects on breast health. According to the human studies, we found that Cd could be responsible for the development and progression of malignant breast tumors due to markedly higher levels in clinical matrices of cases (whole blood, urine, breast tissue, keratin materials) than in clinical matrices of controls. Cadmium does not appear to affect BC density. In contrast, Cd has been found to have a detrimental effect on sex hormones, disrupting the balance of estrogen and androgen. We found that studies looking at dietary Cd intake and BC risk generally (without measuring urine or blood Cd) do not support the association between dietary Cd intake and BC risk. In notable contrast, studies looking at dietary Cd intake and BC risk by measuring Cd in urine or blood generally support this association. The effect of airborne Cd on BC risk was weak, but in favor of specific histological forms, primarily ER-/PR- invasive tubular breast carcinomas. Regardless of the intake route of Cd into the body, it can be concluded that Cd has a harmful effect on breast health. However, well-designed longitudinal, mechanistic, meta-analytic, and other studies are urgently needed to confirm the exact role of environmental Cd in breast carcinogenesis. © 2025 The Authors

Breast cancer (BC) is a multifactorial disease with unresolved etiology. Environmental pollutants, primarily trace metals, play a pivotal role in the pathophysiological cascade of malignant tumors, including BC. In this up-to-date review, we comprehensively and critically examined the relationship between cadmium (Cd) and BC. For this purpose, peer-reviewed studies from relevant databases (PubMed, SCOPUS, and Cochrane Library) over the last 40 years were retrieved and analyzed. We found that in vitro and in vivo studies strongly support the view that Cd has harmful effects on breast health. According to the human studies, we found that Cd could be responsible for the development and progression of malignant breast tumors due to markedly higher levels in clinical matrices of cases (whole blood, urine, breast tissue, keratin materials) than in clinical matrices of controls. Cadmium does not appear to affect BC density. In contrast, Cd has been found to have a detrimental effect on sex hormones, disrupting the balance of estrogen and androgen. We found that studies looking at dietary Cd intake and BC risk generally (without measuring urine or blood Cd) do not support the association between dietary Cd intake and BC risk. In notable contrast, studies looking at dietary Cd intake and BC risk by measuring Cd in urine or blood generally support this association. The effect of airborne Cd on BC risk was weak, but in favor of specific histological forms, primarily ER-/PR- invasive tubular breast carcinomas. Regardless of the intake route of Cd into the body, it can be concluded that Cd has a harmful effect on breast health. However, well-designed longitudinal, mechanistic, meta-analytic, and other studies are urgently needed to confirm the exact role of environmental Cd in breast carcinogenesis. © 2025 The Authors

The status of essential and toxic trace metals in the blood of Crohn’s disease (CD) patients is unexplained. This study aimed to provide the first elemental profiling of the most recognized essential elements (Mn, Cu, Zn, Se) and selected toxic trace elements (As, Cd, Pb, and U) in sera and cell lysate (CL) samples of CD patients (n = 84). The results were compared with sex- and age-matched samples from the control group (CG). CD sera contained significantly higher levels of Mn, As, Cd, Pb, and U than did CG sera. An identical pattern, with the added inclusion of Cu (also higher in CD patients than in the CG), was obtained for CL samples. However, the most important finding was hypermanganesemia, which indicates that Mn could act as a toxic trace metal in CD. As, Cd, and U were the most significant toxic elements that showed antagonistic effects on the extrusion of essential Mn and Cu. Circulatory system screening markers for CD are hereby proposed (Mn/Cu, Mn/As, and Mn/Pb ratios). These three metal ratios were strongly and significantly correlated with F-Calprotectin levels, and deserve consideration as new markers of CD. The target metals and metal ratios should be taken into consideration as novel initiating and/or modifying factors for CD. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

The status of essential and toxic trace metals in the blood of Crohn’s disease (CD) patients is unexplained. This study aimed to provide the first elemental profiling of the most recognized essential elements (Mn, Cu, Zn, Se) and selected toxic trace elements (As, Cd, Pb, and U) in sera and cell lysate (CL) samples of CD patients (n = 84). The results were compared with sex- and age-matched samples from the control group (CG). CD sera contained significantly higher levels of Mn, As, Cd, Pb, and U than did CG sera. An identical pattern, with the added inclusion of Cu (also higher in CD patients than in the CG), was obtained for CL samples. However, the most important finding was hypermanganesemia, which indicates that Mn could act as a toxic trace metal in CD. As, Cd, and U were the most significant toxic elements that showed antagonistic effects on the extrusion of essential Mn and Cu. Circulatory system screening markers for CD are hereby proposed (Mn/Cu, Mn/As, and Mn/Pb ratios). These three metal ratios were strongly and significantly correlated with F-Calprotectin levels, and deserve consideration as new markers of CD. The target metals and metal ratios should be taken into consideration as novel initiating and/or modifying factors for CD. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

The purpose of this study was to establish reference values (RVs) for the occupationally- and environmentally-important toxic elements in the whole blood of adult Serbian population for the first time. Contaminated drinking water with arsenic, high share of smokers in the country, removing tetraethyl lead from the gasoline and war attack at the end of the twentieth century were some of the reasons to provide background information for arsenic (As), cadmium (Cd), lead (Pb), thorium (Th), and uranium (U) in the blood of the Serbian population. The whole blood samples were collected from the healthy respondents living in the Belgrade and surrounding areas of the capital (n = 305; w/m ratio = 154/151; mean age: 41 ± 2). The concentrations of toxic metals were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Reference values were estimated as the lower limit (LL) and upper limit (UL) of the 95% confidence interval (CI), together with the selected percentiles (P2.5-P97.5). The obtained geometric mean (GM) for As, Cd, Pb, Th, and U were: 0.50 ng/g, 0.32 ng/g, 20.94 ng/g, 0.30 ng/g, and 0.06 ng/g, respectively. The influences of age, sex and lifestyle on results were considered. Women have significantly higher levels of Cd and Th than men. The increased level of Th was observed in the aged group below 40 years, while smokers had significantly higher levels of Pb and double higher level of Cd in the blood than non-smokers (p < 0.05). In comparison with other population groups worldwide, the Serbian population had significantly higher levels of Th and U (up to 100 times higher). These findings could contribute to better understanding of the molecular basis for the development of various health hazards, including the increased incidence of cancer among the Serbian population which need be confirmed by clinical studies. © 2018 Elsevier Inc.

The purpose of this study was to establish reference values (RVs) for the occupationally- and environmentally-important toxic elements in the whole blood of adult Serbian population for the first time. Contaminated drinking water with arsenic, high share of smokers in the country, removing tetraethyl lead from the gasoline and war attack at the end of the twentieth century were some of the reasons to provide background information for arsenic (As), cadmium (Cd), lead (Pb), thorium (Th), and uranium (U) in the blood of the Serbian population. The whole blood samples were collected from the healthy respondents living in the Belgrade and surrounding areas of the capital (n = 305; w/m ratio = 154/151; mean age: 41 ± 2). The concentrations of toxic metals were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Reference values were estimated as the lower limit (LL) and upper limit (UL) of the 95% confidence interval (CI), together with the selected percentiles (P2.5-P97.5). The obtained geometric mean (GM) for As, Cd, Pb, Th, and U were: 0.50 ng/g, 0.32 ng/g, 20.94 ng/g, 0.30 ng/g, and 0.06 ng/g, respectively. The influences of age, sex and lifestyle on results were considered. Women have significantly higher levels of Cd and Th than men. The increased level of Th was observed in the aged group below 40 years, while smokers had significantly higher levels of Pb and double higher level of Cd in the blood than non-smokers (p < 0.05). In comparison with other population groups worldwide, the Serbian population had significantly higher levels of Th and U (up to 100 times higher). These findings could contribute to better understanding of the molecular basis for the development of various health hazards, including the increased incidence of cancer among the Serbian population which need be confirmed by clinical studies. © 2018 Elsevier Inc.