Trace Elements in Medicine and Biology

Strontium stimulates alkaline phosphatase and bone morphogenetic protein-4 expression in rat chondrocytes cultured in vitro Publication date: September 2019 Source: Journal of Trace Elements in Medicine and Biology, Volume 55 Author(s): Jinfeng Zhang, Xiaoyan Zhu, Yezi Kong, Yan Huang, Xukun Dang, Linshan Mei, Baoyu Zhao, Qing Lin, Jianguo Wang Abstract The trace element strontium has a significant impact on cartilage metabolism. However, the direct effects of strontium on alkaline phosphatase (ALP), a marker of bone growth, and bone morphogenetic protein-4 (BMP-4), which plays a key role in the regulation of bone and cartilage development, are not entirely clear. In order to understand the mechanisms involved in these processes, the chondrocytes were isolated from Wistar rat articular cartilage by enzymatic digestion and cultured under standard conditions. They were then treated with strontium at 0.5, 1.0, 2.0, 5.0, 20.0 and 100.0 μg/mL for 72 h. The mRNA abundance and protein expression levels of ALP and BMP-4 were measured using real-time polymerase chain reaction (real-time PCR) and Western blot analysis. The results showed that the levels of expression of ALP and BMP-4 in chondrocytes increased as the concentration of strontium increased relative to the control group, and the difference became significant at 1.0 μg/mL strontium (P<0.05). These results indicated that strontium could be involved in cartilage development viaregulating ALP and BMP-4 expression.

Effects of zinc supplementation on serum adiponectin concentration and glycemic control in patients with type 2 diabetes Publication date: September 2019 Source: Journal of Trace Elements in Medicine and Biology, Volume 55 Author(s): Somayyeh Asghari, Mohammad Javad Hosseinzadeh-Attar, Elham Alipoor, Mojtaba Sehat, Mohammad Reza Mohajeri-Tehrani Abstract Background Previous studies have suggested that zinc is involved in insulin homeostasis. Adiponectin is a well-known adipokine with anti-diabetic, anti-atherogenic, and anti-inflammatory properties. The aim of this study was to investigate the effect of zinc supplementation on glycemic control, and the potential mediating role of adiponectin, in patients with type 2 diabetes. Methods In this randomized double-blind placebo-controlled clinical trial, 60 patients with diabetes, 30-60 years, were randomized to receive either 30 mg/d zinc (as zinc gluconate) or placebo for 12 weeks. Circulating levels of adiponectin, zinc, glucose homeostasis parameters, and lipid profiles, as well as anthropometric parameters and dietary intakes, were assessed. Results About 53.3% of the patients had zinc insufficiency at baseline. Serum zinc levels improved significantly in the intervention than control group following 12 weeks supplementation (P < 0.001). Adiponectin (1.23 ± 2.23 μg/ml, P = 0.006) and insulin (3.6 ± 4.66 μIU/ml, P = 0.001) levels increased significantly compared to baseline in the zinc group; but this change was not significant compared with the control group. Following supplementation, there were no significant differences in glycemic control and anthropometric parameters between the two groups. Serum HDL levels increased significantly in the zinc (5.37 ± 14.8 mg/dl) compared to control (-1.53 ± 6.9 mg/dl) group following supplementation (P = 0.039). Conclusion Despite a significant increase in serum zinc level, no improvement was observed in glycemic control, following 12 weeks supplementation with 30 mg/d zinc (as zinc gluconate). Zinc supplementation restored adiponectin concentrations partly within the intervention group, and increased HDL levels compared to the control group. The current findings did not support improvement in glucose homeostasis following zinc supplementation in patients with type 2 diabetes under the present study design.

Dietary boron supplementation enhances sperm quality and immunity through influencing the associated biochemical parameters and modulating the genes expression at testicular tissue Publication date: September 2019 Source: Journal of Trace Elements in Medicine and Biology, Volume 55 Author(s): Binsila B. Krishnan, Sellappan Selvaraju, Nisarani Kollurappa Shivakumar Gowda, Karthik Bhat Subramanya, Dintaran Pal, Santhanahalli Siddalingappa Archana, Raghavendra Bhatta Abstract Introduction Dietary boron improves immune and antioxidant status and calcium metabolism in mammals. However, till date the effects of dietary boron supplementation on male reproduction, especially on sperm production and sperm quality in farm animals are not documented. Objective The present study was aimed to investigate the influence of dietary boron on semen production, semen quality, immunity and molecular changes in the testis, blood and seminal plasma and to assess the interrelationship with other minerals in male goats. Methodology The study was conducted in 21 adult male goats divided into 3 groups (control, boron and selenium supplemented groups, n = 7 each). In boron group, boron was supplemented at 40 ppm and in selenium group, selenium was supplemented at 1 ppm over and above the basal level. In control group, only the basal diet was fed without supplementary boron or selenium. The feeding trial was carried out for 60 days. Selenium was taken as a positive control for the dietary boron supplementation experiment. Following feeding trials, the sperm concentration, kinematics and functional attributes, immunity and molecular level changes in the testis, biomolecular changes in the blood and seminal plasma and also interrelationship with other minerals were studied. Results The average sperm concentration (million/ml) and the total sperm production (million/ejaculate) were significantly (p < 0.05) increased in boron supplemented group when compared to selenium and control groups. The boron levels in blood plasma (r = 0.65) and seminal plasma (r = 0.54) showed a positive correlation with sperm progressive motility. Blood and seminal plasma metabolic biomarker namely, aspartate aminotransferase (AST) (p < 0.01) was significantly lower in the boron and selenium supplemented group than control, while alanine aminotransferase (ALT) (p < 0.05) was significantly lower in the boron supplemented group than selenium and control group. There was a significant increase in the mRNA expression of serine proteinase inhibitor (SERPIN) and interferon γ (IFNγ) in the testis of boron supplemented than the control group. Boron supplementation up-regulated the immune-regulatory gene, interleukin 2 (IL2) and antioxidant gene, catalase (CAT) in the peripheral blood mononuclear cells (PBMC). On contrary, toll-like receptor 2 (TLR2) mRNA expression was significantly (p < 0.05) down-regulated in boron and selenium supplemented groups. Conclusion The study revealed that dietary boron supplementation increased the sperm output, sperm motility and enhanced the immune and antioxidant defense capacity in male goats. The improved semen quality can be attributed to enhanced expression of testicular SERPIN, a crucial protein for the regulation of spermatogenesis process. Graphical abstract Dietary boron supplementation increased the sperm output and sperm motility by modulating the immune mechanism, antioxidant capacity and spermatogenic process in male goats. Blue coloured upright arrow depicts significant increase and down arrow depicts significant decrease of the parameters.

Complementary techniques (spICP-MS, TEM, and HPLC-ICP-MS) reveal the degradation of 40 nm citrate-stabilized Au nanoparticles in rat liver after intraperitoneal injection Publication date: September 2019 Source: Journal of Trace Elements in Medicine and Biology, Volume 55 Author(s): Roberto Álvarez-Fernández García, Nerea Fernández-Iglesias, Carlos López-Chaves, Cristina Sánchez-González, J. Llopis, Maria Montes-Bayón, Jörg Bettmer Abstract Background Due to the increased use of engineered nanoparticles (NPs), their tracing in environmental and biological systems is of utmost importance. Besides their accumulation within a biological specimen, little is known about their degradation and transformation into corresponding low-molecular species that might influence any toxicological impact. Analytical methods Wistar rats underwent intraperitoneal injections of 40 nm citrate-stabilized gold nanoparticles. Different liver samples were analysed for the occurrence of nanoparticles and potential degradation products by means of spICP-MS, TEM and HPLC-ICP-MS. Main findings Studies using spICP-MS revealed the presence of the originally administrated Au NPs (40 nm diameter) and some evidences of other Au-containing species due to the increased background signal. Images obtained by transmission electron microscopy (TEM) showed the predominant presence of particles of significantly smaller diameter (6 ± 2 nm). As complementary method, HPLC-ICP-MS confirmed the presence of both particle types indicating a degradation of the Au NPs accompanied by detection of low-molecular Au species. Conclusions This study underlines that degradation of gold nanoparticles to low-molecular gold species might have to be taken into account in future for studies on their toxicological behaviour and their potential use in clinical applications. Graphical abstract

Lead poisoning due to ingestion of lead-contaminated opium: A diagnostic study on patients’ imaging findings Publication date: September 2019 Source: Journal of Trace Elements in Medicine and Biology, Volume 55 Author(s): Nasim Zamani, Hossein Hassanian-Moghaddam, Hooman Bahrami-Motlagh, Sara Ahmadi, Scott Phillips Abstract Objectives Our study attempts to determine if for patients following ingestion of lead-contaminated opium, radiographs [plain X-ray (KUB)] or unenhanced computed tomography (CT scan) of the abdomen may be predictive of lead poisoning. Methods Our study is concerned with patients of >21 years with elevated lead concentrations, who had undergone KUB or CT. Patients with other toxicities who had undergone similar imaging profiles but who had low blood lead level (BLL) were enrolled as controls. Results We evaluated a total of 79 cases and 79 controls with median [IQR] BLLs of 126 [97.4, 160] μg/dL and 8.7 [5.5, 15] μg/dL. All cases and eleven controls (13.9%) were addicted to oral opium, and of these cases, anemia (94.9%) and abdominal pain (92.4%) were the two most common clinical manifestations. Two radiologists reviewed the X-ray and non-contrast CTs. Fifty (63.3%) and 53 (67.1%) cases and controls underwent CT scanning with 34 (68%) vs. 6 (11.3%) positive CTs (P < 0.001) while 43 (54.4%) and 39 (43.3%) underwent X-rays with 21 (48.8%) vs. 4 (11.8%) positive X-rays, respectively (P < 0.001). Positive CT is associated with BLL between 10 and 45 μg/dL with a specificity of 96.9%, 88.7% and positive predictive value of 97.5% and 85% respectively. Conclusions In suspected cases of lead exposure due to ingested opium, and if BLL is not readily available, a positive imaging result may guide radiologists and physicians to consider lead poisoning.

Heavy metal toxicity: An update of chelating therapeutic strategies Publication date: July 2019 Source: Journal of Trace Elements in Medicine and Biology, Volume 54 Author(s): Jong-Joo Kim, You-Sam Kim, Vijay Kumar Abstract Aim This review illustrates heavy metals toxicity, currently available therapies and the role and efficacy of chelation therapy for its management. Summary Heavy metals are necessary for various biological processes, but they become harmful in excess. Specifically, they induce oxidative stress by generating free radicals and reducing antioxidant levels. Heavy metals also alter the confirmation of protein and DNA and inhibit their function. Chelation therapy is commonly used to treat metals toxicity. Chelation is a chemical process that occurs when interaction between a central metal atom/ion and ligand leads to formation of a complex ring-like structure. The ligand has a donor ion/molecule, which has a lone pair of electrons and may be monodentate to polydentate. Each metal has a different reactivity with a ligand, so a specific chelation agent is required for each metal. Combination therapy with a chelating agent and an antioxidant led to improved outcome. Conclusion Heavy metal poisoning is a common health problem because of mining, smelting, industrial, agricultural and sewage waste. Heavy metals can be efficiently excreted from the body following treatment with proper chelation agents. Graphical abstract

Alterations in membrane fluidity are involved in inhibition of GM-CSF-induced signaling in myeloid cells by zinc Publication date: July 2019 Source: Journal of Trace Elements in Medicine and Biology, Volume 54 Author(s): Isabell Aster, Lisa-Marie Barth, Lothar Rink, Inga Wessels Abstract Zinc has a strong influence on the function of the immune system and is a driving factor for immune cell development. In this regard, studies revealed cell type specific effects of zinc. During zinc deficiency for example, development and activity of myeloid cells seems to be prioritized at the cost of cells from the lymphoid lineage. In T-cells, the altered proliferation was found to be due to zinc’s effect on IL-2-induced signaling processes, but in contrast to lymphoid cells, effects of zinc homeostasis on growth-factor-induced signaling in myeloid cells have not been investigated yet. The granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of the major factors inducing monopoiesis. Considering the structural similarities between the GM-CSF receptor and those of the IL-receptor family as well as a similar set of signaling molecules involved, an impact of zinc on the GM-CSF signaling seems to be likely. Therefore, the effect of zinc on GM-CSF-induced signaling molecules was investigated here, using U937 cells as a model myeloid cell line. GM-CSF stimulation significantly increased STAT5 phosphorylation which was prevented completely by pre-incubation with zinc and pyrithione. U937 cells showed a strong pre-activation regarding c-Raf, which was significantly decreased by zinc and pyrithione incubation, independently from GM-CSF stimulation. As current literature was not sufficient to explain the observed effects, we hypothesized an altered receptor-complex assembly. As membrane composition and plasticity, subsumed under the term of membrane fluidity, was found to affect receptor multimerization, the impact of zinc on membrane fluidity was considered as a completely novel approach. Indeed, addition of zinc also decreased GM-CSFR expression on the cell surface and most interestingly altered membrane fluidity. In conclusion, we hypothesize that the incubation with zinc causes an alteration of membrane fluidity that hinders efficient receptor assembly as well as phosphorylation of signal molecules and therefore signal transduction.

A quick and simple method for the determination of six trace elements in mammalian serum samples using ICP-MS/MS Publication date: July 2019 Source: Journal of Trace Elements in Medicine and Biology, Volume 54 Author(s): Johannes Florian Kopp, Sandra Marie Müller, Gabriele Pohl, Kristina Lossow, Anna Patricia Kipp, Tanja Schwerdtle Abstract In order to assess the individual trace element status of humans for either medical or scientific purposes, amongst others, blood serum levels are determined. Furthermore, animal models are used to study interactions of trace elements. Most published methods require larger amounts (500–1000 μL) of serum to achieve a reliable determination of multiple trace elements. However, oftentimes, these amounts of serum cannot be dedicated to a single analysis and the amount available for TE-determination is much lower. Therefore, a published ICP-MS/MS method for trace element determination in serum was miniaturized, optimized and validated for the measurement of Mn, Fe, Cu Zn, I and Se in as little as 50 μL of human and murine serum and is presented in this work. For validation, recoveries of multiple LOTs and levels from commercially available human reference serum samples were determined, intra- and inter-day variations were assessed and limits of detection and quantification determined. It is shown, that the method is capable of giving accurate and reproducible results for all six elements within the relevant concentration ranges for samples from humans living in central Europe as well as from laboratory mice. As a highlight, the achieved limits of detection and quantification for Mn were found to be at 0.02 μg/L serum and 0.05 μg/L serum, respectively, while using an alkaline diluent for the parallel determination of iodine. Graphical abstract Method development and validation for the determination of six trace elements in 50 μL of mammalian serum using ICP-MS/MS.

Metal(loid)s urinary level among workers of gas refinery and petrochemical companies: Health risk assessment of metal(loid)s in drinking water and dust Publication date: July 2019 Source: Journal of Trace Elements in Medicine and Biology, Volume 54 Author(s): Raheleh Kafaei, Marzieh Rezaei, Mehdi Ahmadi, Rahim Tahmasebi, Sina Dobaradaran, Mohsen Omidvar, Afshin Ostovar, Arezo Savari, Bahman Ramavandi Abstract Background Asalouyeh (southern Iran) contains many pollution sources like petrochemical and gas refinery companies. Few studies were conducted on the body burden of metal(loid)s in occupationally exposed workers of the companies in this area. Objectives The urine concentration of metal(loid)s in workers of gas refinery and petrochemical companies in Asalouyeh (who have been worked as "two weeks work-two weeks rest" schedule) was evaluated during a before-and-after observational study. The risks of metal(loid)s in drinking water and dust particles in the studied area were also assessed. Methods Urinary samples (n = 179) were gathered at the first day of two weeks of work (before) and at the end of two weeks of work (after). The concentration of V, Ni, Mn, Cd, and As was measured using a graphite furnace atomic absorption spectrometry. The health hazards of metal(loid)s in the air dust and drinking water of workers were also evaluated. Results The median concentration of metal(loid)s for workers of gas refinery and petrochemical companies for before and after two weeks of work was measured, respectively, as: As (11.44 and 9.31 μg/L), Ni (1.06 and 0.51 μg/L), Cd (0.36 and 0.31 μg/L), Mn (0.29 and 0.24 μg/L), and V (0.08 and 0.05 μg/L). After two weeks work, the median of all metal(loid)s in the urine of petrochemical and gas refinery workers was significantly increased. The non-cancer risk due to intake metal(loid)s from drinking water was more than the threshold value and the cancer risk from drinking water and inhaled air dust was less than the threshold. Conclusion Our results revealed the effect of gas refinery and petrochemical activities on increasing the metal(loid)s concentration of the worker's body and the necessity to protect this group. Additionally, the metal(loid)s intake from drinking water and inhaled dust posed no cancer risk to the workers.

Soil and indoor dust as environmental media of human exposure to As, Cd, Cu, and Pb near a copper smelter in central Chile Publication date: July 2019 Source: Journal of Trace Elements in Medicine and Biology, Volume 54 Author(s): Maite Berasaluce, Pedro Mondaca, Marta Schuhmacher, Manuel Bravo, Sébastien Sauvé, Claudia Navarro-Villarroel, Elvira A. Dovletyarova, Alexander Neaman Abstract In the present study, we assessed the non-carcinogenic and carcinogenic human health risk due to exposure to trace elements in soil and indoor dust in Puchuncaví valley. We also determined the associations between trace element concentration in hair/toenails and the estimated chronic daily intake of trace elements in soil and indoor dust. We found statistically significant association between the trace element concentration in hair/toenails and the estimated chronic daily intake of soil and indoor dust. Indoor dust was more important than soil in terms of human exposure to trace elements in Puchuncaví, due to the high concentration of trace elements on this environmental media and long periods of time that the population spends at their households. With regards to non-carcinogenic risk, we found that there was no health risk associated to soil and indoor dust exposure in the Puchuncaví valley, because none of the hazard quotient values surpassed 1.0. However, carcinogenic risk due to arsenic exposure was above the threshold value of 1.0E-04 in the population of young children (from 1 to 5 years old) in all studied areas, including the control, and in the population of children (from 6 to <18 years old) in the exposed area. Such risk values are classified as unacceptable (US EPA, 2001), requiring some target intervention from the Chilean government.