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Endoplasmic Reticulum Stress Induced by Toxic Elements-a Review of Recent Developments

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

Endoplasmic reticulum of all eukaryotic cells is a membrane-bound organelle. Under electron microscope it appears as parallel arrays of "rough membranes" and a maze of "smooth vesicles" respectively. It performs various functions in cell, i.e., synthesis of proteins to degradation of xenobiotics. Bioaccumulation of drugs/chemicals/xenobiotics in the cytosol can trigger ER stress. It is recognized by the accumulation of unfolded or misfolded proteins in the lumen of ER. Present review summarizes the present status of knowledge on ER stress caused by toxic elements, viz arsenic, cadmium, lead, mercury, copper, chromium, and nickel. While inorganic arsenic may induce various glucose-related proteins, i.e., GRP78, GRP94 and CHOP, XBP1, and calpains, cadmium upregulates GRP78. Antioxidants like ascorbic acid, NAC, and Se inhibit the expression of UPR. Exposure to lead also changes ER stress related genes, i.e., GRP 78, GRP 94, ATF4, and ATF6. Mercury too upregulates these genes. Nickel, a carcinogenic element upregulates the expression of Bak, cytochrome C, caspase-3, caspase-9, caspase-12, and GADD 153. Much is not known on ER stress caused by nanoparticles. The review describes inter-organelle association between mitochondria and ER. It also discusses the interdependence between oxidative stress and ER stress. A cross talk amongst different cellular components appears essential to disturb pathways leading to cell death. However, these molecular switches within the signaling network used by toxic elements need to be identified. Nevertheless, ER stress especially caused by toxic elements still remains to be an engaging issue.

Metals and Metalloids Release from Orthodontic Elastomeric and Stainless Steel Ligatures: In Vitro Risk Assessment of Human Exposure

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

Elastomeric ligatures are increasingly used as a part of esthetic orthodontic treatment, particularly in children. The aim of the present study was to experimentally test whether these appliances may contribute to exposure to toxic elements. In the present study, elastomeric ligatures (ELs) were incubated in artificial human saliva for 1 month (a typical period of their use) and the release of 21 metals (Ba, Cd, Co, Cr, Cu, Fe, Li, Mn, Mg, Mo, Ni, Pb, Rb, Tl, Ti, Sb, Sr, Sn, Zn, U, V) and 2 metalloids (As and Ge) was studied using inductively coupled plasma-mass spectrometry. For comparison, stainless steel ligatures (SLs) were incubated for 1, 3, and 6 months (since sometimes their use is prolonged) under similar conditions. The determined metal levels were compared to the corresponding safety limits for human exposure. During 1 month, the ELs released Cd, Co, Cr, Mn, Ni, and Sn at total mean +/- SD level of 0.31 +/- 0.09, 0.98 +/- 0.30, 3.96 +/- 1.31, 14.7 +/- 8.5, 13.8 +/- 4.8, and 49.5 +/- 27.7 mu g, respectively. Other elements were always below the detection limits. In case of SL, the release of Co, Cr, Fe, Ni, Mn, and Sn was observed, and the determined values increased over the studied period. After 6 months, their total mean +/- SD levels amounted to 28.6 +/- 0.2, 21.7 +/- 0.2, 623.5 +/- 3.0, 1152.7 +/- 1.8, 5.5 +/- 0.3, and 22.6 +/- 0.2 mu g, respectively. The released metal levels from both ligature types were always below safety limits. The release of Ni from SL during 6 months would constitute 5.0 and 11.5% of tolerable intake in adults and children, respectively. The results of this in vitro study highlight that the use of ligatures in orthodontic treatment can be considered safe in terms of metal exposure although elastic ligatures replaced on a monthly basis appear to be advantageous in comparison to the prolonged use of stainless steel appliances.

Trace Elements in the Lung Tissue Affected by Sarcoidosis

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

In the lungs of 76 patients with verified sarcoidosis, 28 chemical elements were identified with neutron activation analysis. High levels of Ca, Fe, Cr, Co, Cs, Eu, Lu, Th, Hf, Au, and U and low level of Na compared to the control samples were determined in sarcoidosis. There were no significant differences in the content of Zn, Rb, La, Sm, Sr, Nd, As, Br, Ag, Tb, Sc, Ta, Sb, Ba, and Yb. Spearman correlation analysis shows multiple positive associations, with the maximum being in pairs as follows: Fe-Cr, Eu-La, Ce-Lu, Hf-Cr, Sc-Zn, Fe-Hf, Ce-Co, and Sb-Cr. These studies support the hypothesis that sarcoidosis is a response of the organism in the form of granulomatous inflammation when exposed to heavy metals and rare earth elements in the environment. We assume that the role of calcium and iron is to separate granulomas from the tissues of the body.

Ionizing Radiation Exacerbates the Bone Loss Induced by Iron Overload in Mice

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

Patients with radiotherapy are at significant risks of bone loss and fracture. On the other hand, osteoporosis often occurs in disorders characterized by iron overload. Either ionizing radiation (IR) or iron overload alone has detrimental effects on bone metabolism, but their combined effects are not well defined. In this study, we evaluated the effects of IR on bone loss in an iron-overload mouse model induced by intraperitoneal injection of ferric ammonium citrate (FAC). In the present study, we found that IR additively aggravated iron overload induced by FAC injections. Iron overload stimulated hepcidin synthesis, while IR had an inhibitory effect and even inhibited the stimulatory effects of iron overload. Micro-CT analysis demonstrated that the loss of bone mineral density and bone volume, and the deterioration of bone microarchitecture were greatest in combined treatment group. Iron altered the responses of bone cells to IR. Iron enhanced the responses of osteoclasts to IR with elevated osteoclast differentiation, but did not affect osteoblast differentiation. Our study indicates that IR and iron in combination lead to a more severe impact on the bone homeostasis when compared with their respective effects. IR aggravated iron overload induced bone loss by heightened bone resorption relative to formation. The addictive effects may be associated with the exacerbated iron accumulation and osteoclast differentiation.

ICP-MS Assessment of Hair Essential Trace Elements and Minerals in Russian Preschool and Primary School Children with Attention-Deficit/Hyperactivity Disorder (ADHD)

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

The objective of the present study was to investigate the relationship between hair essential trace element and mineral content and ADHD in preschool (4-6 years old) and primary school children (6-10 years old) in relation to age and gender. Hair essential trace element and mineral content in 90 Russian children with ADHD and 90 age- and gender-matched neurotypical controls were assessed using inductively coupled plasma mass-spectrometry after microwave digestion. The obtained data demonstrate that hair Co, Cu, Mn, Si, and Zn contents in ADHD children was significantly reduced by 18%, 10%, 27%, 16%, and 19% as compared to the control values, respectively. The most significant decrease in children with ADHD was observed for hair Mg levels, being 29% lower than those in neurotypical children. After adjustment for age and gender, the observed difference in hair element content was more characteristic for preschool children and girls, respectively. Multiple linear regression analysis demonstrated that in a crude model (hair element levels as predictors), only hair Zn content was significantly inversely associated with ADHD (beta = - 0.169; p = 0.025). Adjustment for anthropometric parameters (model 2) did not increase the predictive ability of the model, although it improved the association between hair Zn and ADHD in children (beta = - 0.194; p = 0.014). Hypothetically, the observed alterations may at least partially contribute to neurobehavioral disturbances in children with ADHD. Moreover, the results of the present study raise the question about the potential benefits of Zn and Mg supplementation in children with ADHD. However, further detailed studies are required to investigate micronutrient deficiencies in ADHD.

Association Between Thyroid Hormone Status and Trace Elements in Serum of Patients with Nodular Goiter

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

The present study investigated the status of calcium and magnesium as well as essential trace elements including iodine, selenium, copper, iron, and zinc in adults residing in the Zhytomyr region of Ukraine. In addition, the relative risk of goiter occurrence was evaluated. In this comparative study, 40 adults without goiter (control group) and 16 adults with diagnosed nodular goiter (NG) were examined. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used for the measurements of Mg, Ca, Se, Zn, Cu, and Fe in serum of patients with NG and control group. Patients with nodular goiter had lower serum values of Ca, Mg, Se, Cu, Fe, and Zn than those in the control group. The presence of mild iodine deficiency was evident in both groups with the median urinary iodine excretion (UIE) 80.5 mu g/L in the control group and 64.5 mu g/L in goiter group. There was a positive association between goiter presence and low concentration of Ca in serum (odds ratio (OR) = 2.29 (1.26-3.55), p < 0.05) in the NG group. High relative risk of goiter was observed at low concentrations of magnesium (OR = 3.33 (1.39-7.62), p < 0.05) and selenium (OR = 1.63, (1.16-1.78), p < 0.05) in comparison with OR values in the control group. Low concentrations of Ca, Mg, Zn, and Se in serum combined with reduced UIE resulted in the highest risk of goiter (OR = 12.5, (2.15-79.42), p < 0.01). This study proved that Thyroglobulin concentration in serum is the reliable indicator of nodular goiter. We also suggest that a combination of low concentrations of Ca, Mg, Zn, Cu, and Se in blood serum, and reduced iodine concentration in urine resulted in the highest risk of nodular goiter development.

Variations in the Metallic Ion Concentration in the Silk Gland and Cocoon of Silkworm Antheraea assamensis helfer

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

The natural spinning process in silkworms involves the conformation transition of the liquid silk protein present in the silk gland to make fiber. This conformation transition is influenced by different factors, and some studies suggested that changes in the metallic ion concentrations is one of them (Zhou et al. 2005). This study investigated the changes in the metallic ion compositions in the silk glands (before and during spinning) and cocoons of non-mulberry silkworm Antheraea assamensis helfer. Intact silk glands were dissected from mature 5th instar A. assamensis larvae. The glands were rinsed with deionized water and divided into five divisions: posterior silk gland (PSG), middle silk gland (MSG), anterior silk gland (ASG), posterior middle (PM) and anterior middle (AM) division of silk gland. Cocoon pieces and the gland parts were dried and digested in acid mixture to quantify the metallic contents in an atomic absorption spectrophotometer (Shimadzu, AA7000). We determined seven metals (Na, K, Mg, Ca, Cu, Zn, Fe) present in the different parts of the secretory pathway as well as in the fibers of A.assamensis. Our results suggested that the concentrations of Mg, Ca, Na, and K were more abundant in the gland than the Cu and Zn. Fe concentration was found comparatively less in amount in the gland. Amount of Ca found to be higher in the cocoons. The differences in the metallic ion concentrations in the gland parts before and during spinning suggested the possibility of their role in the formation of silk thread from luminal silk.

The Role of Magnesium in Pathophysiology and Migraine Treatment

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

Migraine is one of the most common recurrent types of headache and is the seventh cause of disability. This neurological disorder is characterized by having pain in head and other various symptoms such as nausea, emesis, photophobia, phonophobia, and sometimes visual sensory disorders. Magnesium (Mg) is a necessary ion for human body and has a crucial role in health and life maintenance. One of the main roles of Mg is to conserve neurons electric potential. Therefore, magnesium deficiency can cause neurological complications. Migraine is usually related to low amounts of Mg in serum and cerebrospinal fluid (CSF). Deficits in magnesium have significant role in the pathogenesis of migraine. Mg has been extensively used in migraine prophylaxis and treatment. This review summarizes the role of Mg in migraine pathogenesis and the potential utilizations of Mg in the prevention and treatment of migraine with the emphasis on transdermal magnesium delivery.

Challenges in the Measurement and Interpretation of Serum Titanium Concentrations

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

The measurement of circulating metal ion levels in total hip arthroplasty patients continues to be an area of clinical interest. National regulatory agencies have recommended measurement of circulating cobalt and chromium concentrations in metal-on-metal bearing symptomatic total hip arthroplasty patients. However, the clinical utility of serum titanium (Ti) measurements is less understood due to wide variations in reported values and methodology. Fine-scale instrumentation for detecting in situ Ti levels continues to improve and has transitioned from graphite furnace atomic absorption spectroscopy to inductively coupled plasma optical emission spectrometry or inductively coupled plasma mass spectrometry. Additionally, analytical interferences, variable sample types, and non-standardized sample collection methods complicate Ti measurement and underlie the wide variation in reported levels. Normal reference ranges and pathologic ranges for Ti levels remain to be established quantitatively. However, before these ranges can be recognized and implemented, methodological standardization is necessary. This paper aims to provide background and recommendations regarding the complexities of measurement and interpretation of circulating Ti levels in total hip arthroplasty patients.

Ferric-Induced Pancreatic Injury Involves Exacerbation of Cholinergic and Proteolytic Activities, and Dysregulation of Metabolic Pathways: Protective Effect of Caffeic Acid

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

The protective effect of caffeic acid on ferric-induced pancreatic injury was investigated using ex vivo and in silico models. Incubation of pancreatic tissues with Fe2+ led to significant depleted levels of glutathione (GSH) and SOD and catalase activities, with concomitant elevated levels of malondialdehyde (MDA) and nitric oxide (NO) and acetylcholinesterase and alpha-chymotrypsin activities. Treatment with caffeic acid led to significant reversion of these levels and activities. Molecular docking revealed a higher binding affinity of caffeic acid with acetylcholinesterase via hydrogen bonding, Pi-Pi stacking, and Van der Waals interactions. FTIR spectroscopy of pancreatic metabolite revealed little or no effect by caffeic acid on functional groups in ferric-induced injured pancreas. The LC-MS analysis of the metabolites revealed Fe2+ caused a 20% depletion of the normal metabolites, with concomitant generation of glyceraldehyde and 3,4-dihydroxymandelaldehyde. Treatment with caffeic acid led to the restoration of TG(22:4(7Z,10Z,13Z,16Z)/24:0/22:5(7Z,10Z,13Z,16Z,19Z)) and dTDP-d-glucose, while depleting glyceraldehyde as well as activating gluconeogenesis. These results indicate the ability of caffeic acid to protect against ferric toxicity by exacerbating antioxidative activities, with concomitant inhibition of MDA and NO levels while deactivating metabolic pathways linked to oxidative stress.

The Efficacy of Imipenem Conjugated with Synthesized Silver Nanoparticles Against Acinetobacter baumannii Clinical Isolates, Iran

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

Carbapenem-resistant Acinetobacter baumannii (CRAB) remains as a serious cause of infectious diseases and septic mortality in hospitalized patients worldwide. This study was conducted to evaluate the antimicrobial effect of imipenem conjugated silver nanoparticles (AgNPs) on resistant isolated A. baumannii from nosocomial infections. The antimicrobial susceptibility test of 100 A. baumannii clinical isolates against different antibiotics was performed. PCR was used to confirm bacterial resistance and to identify different genes encoding Ambler class beta-lactamases. The chemically synthesized AgNPs were characterized using UV-vis spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier-transform infrared (FTIR). The stability, drug release kinetic, and cytotoxicity (MTT assay) of AgNPs were also investigated. The imipenem were conjugated with AgNPs, and conjugants were characterized as discussed above. Minimum inhibitory concentration (MIC) of the AgNPs and conjugants were tested against A. baumannii isolates and compared with imipenem alone. The results revealed that among all isolated A. baumannii, 76% showed resistant to imipenem (MIC >= 64 mu g/mL to >= 256 mu g/mL). The bla(OXA-23), bla(PER), bla(OXA-40), and bla(IMP) genes were the most prevalent genes. UV-vis spectroscopy, XRD, TEM, and FTIR analysis confirmed synthesis of AgNPs (average size of 10-40 nm) and conjugation with imipenem. The release of imipenem from AgNPs can be defined as Fickian diffusion model. The MIC values of AgNPs conjugated with imipenem against resistant A. baumannii were decreased in a dose dependent manner and were based on existence of resistant genes. The AgNPs also showed low cytotoxic effects. The results suggest that imipenem-AgNPs has a strong potency as a powerful antibacterial agent against multi-resistant A. baumannii.

Grape Seed Proanthocyanidin Extract Mitigates Titanium Dioxide Nanoparticle (TiO2-NPs)-Induced Hepatotoxicity Through TLR-4/NF-kappa B Signaling Pathway

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

With the progress of nanotechnology, the adverse effects of nanoscale materials are receiving much attention. Inhibition of toll-like receptor 4 (TLR-4)/nuclear factor kappa B (NF-kappa B) signaling is a hallmark for downregulating the expression of many inflammatory genes implicated in oxidative stress. Therefore, the present study aimed to demonstrate the influence of grape seed proanthocyanidin extract (GSE) on the hepatic TLR-4/ NF-kappa B signaling pathway in TiO2-NP-induced liver damage in rats. Forty male Albino rats were divided into 4 groups (n = 10): G1 was used as a control, G2 received TiO2-NPs (500 mg/kg/day orally) from the 17th to 30th day (acute toxicity), G3 received GSE (75 mg/kg/day orally) for 30 days, and G4 pre- and co-treated with GSE (for 30 days) and TiO2-NPs (from the 17th to 30th day), with the aforementioned doses. TiO2-NPs induced severe hepatic injury that was indicated by biochemical alterations in serum liver markers (acetylcholinesterase, ALT, ALP, total proteins, albumin, and direct bilirubin), oxidative stress indicators (MDA, GSH, and catalase), and histopathological alterations as well. Moreover, TiO2-NPs triggered an inflammatory response via the upregulation of TLR-4, NF-kappa B, NIK, and TNF-alpha mRNA expressions. Pre- and co-treatments with GSE alleviated the detrimental effects of TiO2-NPs which were enforced by the histopathological improvements. These results indicated that GSE effectively protected against TiO2-NP-induced hepatotoxicity via the inhibition of TLR-4/NF-kappa B signaling and hence suppressed the production of pro inflammatory cytokines such as TNF-alpha and improved the antioxidant status of the rats.

The Chronic Use of Magnesium Decreases VEGF Levels in the Uterine Tissue in Rats

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

Vascular endothelial growth factor (VEGF) is the most important regulator of angiogenesis which serves to provide sufficient blood supply, and can trigger both physiological and pathological angiogenesis. Recent studies have shown that VEGF increases in gynecological diseases (such as endometriosis, ovarian, and endometrial cancers) and is a prognostic factor in these pathologies. Therefore, VEGF should be maintained at appropriate levels. Magnesium is used in many gynecological practices (such as eclampsia, preeclampsia, dysmenorrhea, and climacteric symptoms) and the mechanisms of action are still under investigation. Redox status, which can be regulated by magnesium, was shown to affect VEGF expression. The aim of this study was to evaluate the effects of chronic magnesium use on VEGF and oxidative status in the uterus. Magnesium sulfate was administered to rats at doses of 30 mg/kg (intramuscular) for 2 weeks. VEGF, Superoxide dismutase (SOD), Glutathione peroxidase (GPx), and Malondialdehyde (MDA) levels were measured using ELISA; vascular and cellular alterations were determined by histology in the uterine tissue at the metoestrus phase. In the uterine tissue of Mg-treated subjects, magnesium levels increased while VEGF, SOD, GPx, and MDA levels decreased without histological changes. There was a negative correlation between uterine tissue magnesium levels and VEGF, SOD, GPx, and MDA levels. Consequently, the results of this study demonstrated that regular magnesium use decreased VEGF levels in uterus. Decreased VEGF levels were associated with decreased uterine oxidative stress. Chronic magnesium usage may protect the uterine tissue from certain diseases in which angiogenesis is critical.

Dietary Intake and Urinary Excretion of Manganese in Korean Healthy Adults

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

Manganese (Mn) is an essential element for the body's composition and is required for various functions, including nutrient metabolism, immune system function, and antioxidant ability. However, there are insufficient data on the nutritional status of Mn. In this study, we aimed to analyze the relationship between Mn intake and urinary excretion in Korean adults. A twice dietary intake survey using a 24-h recall method was conducted on 640 adults (320 men and 320 women), aged 20 to 69 years. Eighty 24-h urine samples were also twice collected and urinary Mn excretions were analyzed. Results indicated that total Mn intake per day was 4.1 mg for men and 3.9 mg for women (p < 0.05). Mn intake per 1000 kcal of energy consumption was significantly higher in women than in men (2.0 mg/1,000 kcal vs. 2.2 mg/1000 kcal, p < 0.01). Additionally, Mn intake as a percentage of Adequate Intake was 103.0% for men and 110.3% for women (p < 0.05). Mn was mostly consumed from cereals (1.78 mg/day for men and 1.53 mg/day for women), followed by vegetables, seasonings, fruits, and pulses. The main food sources of Mn were rice (27.8% for men, 22.0% for women), kimchi (3.5% for men, 1.4% for women), and tofu (2.8% for men, 2.3% for women); the percentage of Mn consumed from 20 types of foods was 55.6% (women) to 60.4% (men). Urinary Mn excretion was negatively correlated with Mn intake from cereals and positively with mushrooms only for women after adjusting for confounding factors (p < 0.05). In conclusion, dietary Mn intake by Korean adults was adequate to meet the Dietary Reference Intake, but the relationship between Mn intake and urinary excretion was not clear.

Sodium Selenite Improves In Vitro Maturation of Bos primigenius taurus Oocytes

期刊: BIOLOGICAL TRACE ELEMENT RESEARCH, 0; ()

Selenium (Se) is an essential trace element with important functions in animals and whose deficiency is associated with reproductive failures. The aim of this study was to investigate the effect of Se concentrations during in vitro maturation (IVM) of Bos taurus oocyte within the reference ranges for Se status in cattle. For this purpose, Aberdeen Angus cumulus-oocyte complexes (COCs) were matured in IVM medium supplemented with 0, 10, 50, and 100 ng/mL Se (control, deficient, marginal, and adequate, respectively). The results demonstrated that marginal and adequate Se concentrations added during IVM increased viability and non-apoptotic cumulus cells (CC). Moreover, the addition of Se to culture media decreased malondialdehyde level in COC with all studied concentrations and increased total glutathione content in CC and oocytes with 10 ng/mL Se. On the other hand, total antioxidant capacity of COC, nuclear maturation, and the developmental capacity of oocytes were not modified by Se supplementation. However, 10 ng/mL Se increased hatching rate. In conclusion, supplementation with 10 ng/mL Se during in vitro maturation of Bos primigenius taurus oocytes should be considered to improve embryo quality.

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