MOLYBDENUM TOXICOLOGY
- M. Hays, K. Macey, D. Poddalgoda, M. Lu, A. Nong, and L. L. Aylward,Biomonitoring Equivalents for Molybdenum (vol 77, pg 223, 2016), Regulatory Toxicology and Pharmacology, 2022, 134.
02 Association Between Essential and Non-essential Metals, Body Composition, and Metabolic Syndrome in Adults
Growing evidence indicates that metal exposure is associated with metabolic syndrome [a combination of diabetes, high blood pressure (hypertension) and obesity] (MetS); however, mixed results have been reported. The aim of this study was to clarify associations of exposure to essential and non-essential metals with body composition and risks of obesity and MetS. Anthropometry and blood biochemistry of metabolic parameters were obtained from 150 middle-aged Taiwanese adults. Plasma metals were assessed using inductively coupled plasma mass spectrometry, and body compositions were measured by a bioelectrical impedance analysis (BIA). The essential metals of copper (Cu), manganese (Mn), and chromium (Cr) were positively correlated with the body fat mass but inversely correlated with the skeletal muscle mass (all p < 0.05). An adjusted logistic regression showed that Mn [odds ratio (OR) = 1.624 (95% confidence interval 1.072, 2.462), p = 0.02] and, to a lesser extent, Cu [OR = 1.501 (0.985, 2.292), p = 0.059] predicted abdominal obesity, while plasma Cu [OR = 2.211 (1.146, 4.266), p = 0.02] and zinc (Zn) [OR = 2.228 (1.048, 4.736) p = 0.04] predicted MetS. Significant correlations [odds ratio OR, 95% confidence interval] between dyslipidemia [imbalance of lipids such as cholesterol, low-density lipoprotein cholesterol, (LDL-C), triglycerides, and high-density lipoprotein (HDL)] and lithium [OR = 1.716 (1.080, 2.726)], Cu [OR = 2.210 (1.415, 3.454)], Mn [OR = 2.200 (1.320, 3.666)], molybdenum [OR = 1.853 (1.160, 2.958)], and Zn [OR = 1.993 (1.186, 3.349)], and between boron [OR = 2.583 (1.137, 5.868)] and hyperglycemia were observed (all p < 0.05). Exposure to essential metals may affect the body composition and metabolic profiles, exacerbating the risk of MetS.
- J. Ngu, A. V. Skalny, A. A. Tinkov, C. S. Tsai, C. C. Chang, Y. K. Chuang, V. N. Nikolenko, D. A. Zotkin, C. F. Chiu, and J. S. Chang,Association Between Essential and Non-essential Metals, Body Composition, and Metabolic Syndrome in Adults, Biol Trace Elem Res, 2022, 200, 4903-4915.
[“An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B, or equivalently (due to symmetry), the ratio of the odds of B in the presence of A and the odds of B in the absence of A. Two events are independent if and only if the OR equals 1, i.e., the odds of one event are the same in either the presence or absence of the other event. If the OR is greater than 1, then A and B are associated (correlated) in the sense that, compared to the absence of B, the presence of B raises the odds of A, and symmetrically the presence of A raises the odds of B. Conversely, if the OR is less than 1, then A and B are negatively correlated, and the presence of one event reduces the odds of the other event.
Note that the odds ratio is symmetric in the two events, and there is no causal direction implied (correlation does not imply causation): an OR greater than 1 does not establish that B causes A, or that A causes B.[1]”] https://en.wikipedia.org/wiki/Odds_ratio
02 A systematic review and meta-analysis of the hyperuricemia risk from certain metals
The relationship between exposure to certain metals and the risk of hyperuricemia (HUA)[ elevated uric acid level in the blood] has biological plausibility, yet prior studies have presented inconsistent findings. We aim to clarify the relationship between exposure to certain metals and HUA using a systematic review and meta-analysis approach. We searched the Web of Science, Embase, MEDLINE, Pubmed, Corchrane and China National Knowledge Infrastructure databases from inception through December, 2021 in order to identify studies that assessed the relationships between metals and the risk of HUA. Data were pooled by random-effects models and expressed as pooled odds ratios (OR) and 95% confidence intervals (CIs). The risk of bias was assessed using a tool from Agency for Healthcare Research and Quality (AHRQ). Twenty eligible articles (nineteen cross-sectional studies and one cohort) were included in our analysis, involving 63,283 participants in total. The studies showed that arsenic (pooled OR = 1.702, 95% CI: 1.44, 2.011; n = 6, I(2) = 29.5%), calcium (pooled OR = 1.765, 1.111, 2.804; 4, 82.3%), cadmium (pooled OR = 1.199,1.020, 1.410; 11, 38.5%) and lead (pooled OR = 1.564,1.205, 2.030; 11, 72.9%) exposure were, all linked to an increased risk of HUA. Exposure to molybdenum (pooled OR = 0.804, 0.724, 0.975, 3, 0%) was linked to a decreased risk of HUA, however. Exposure to arsenic, calcium, cadmium and lead is associated with an increased risk of HUA. Molybdenum exposure was associated with a decreased prevalence of HUA; however, aluminum, cobalt, copper, iron, magnesium, manganese, mercury, selenium, thallium and zinc are not associated with HUA risk. Further experimental studies are warranted to decipher the mechanisms by which exposure to the above metals affect HUA risk. The findings reinforced the importance of metals in the HUA risk, and provided a reference for legislation to prevent HUA and protect people's health.
- Gu, G. Cao, M. Luo, N. Zhang, T. Xue, R. Hou, and M. Leng,A systematic review and meta-analysis of the hyperuricemia risk from certain metals, Clin Rheumatol, 2022, 41, 3641-3660.
MOLYBDATE− Nontuberculous mycobacterial infection and environmental molybdenum in persons with cystic fibrosis: a case-control study in Colorado
RATIONALE: Nontuberculous mycobacteria NTM are ubiquitous environmental bacteria that may cause chronic lung disease and are one of the most difficult-to-treat infections among persons with cystic fibrosis pwCF . Environmental factors likely contribute to increased NTM densities, with higher potential for exposure and infection. OBJECTIVE: To identify water-quality constituents that influence odds of NTM infection among pwCF in Colorado. METHODS: We conducted a population-based nested case-control study using patient data from the Colorado CF Center NTM database. We associated data from pwCF and water-quality data extracted from the Water Quality Portal to estimate odds of NTM infection. Using Bayesian generalized linear models with binomial-distributed discrete responses, we modeled three separate outcomes; any NTM infection, infections due to Mycobacterium avium complex species, and infections due to M. abscessus group species. RESULTS: We observed a consistent association with molybdenum in the source water and M. abscessus group species infection among pwCF in all models. For every 1-unit increase in the log concentration of molybdenum in surface water, the odds of infection for those with M. abscessus group species compared to those who were NTM culture-negative increased by 79%. The odds of M. abscessus group infection varied by county; the counties with the highest probability of infection are located along the major rivers. CONCLUSIONS: We have identified molybdenum in the source water as the most predictive factor of M. abscessus group infection among pwCF in Colorado. This finding will help inform patients at risk for NTM of their relative risks in residing within specific regions.
E. M. Lipner, J. L. Crooks, J. French, M. Strong, J. A. Nick, and D. R. Prevots,Nontuberculous mycobacterial infection and environmental molybdenum in persons with cystic fibrosis: a case-control study in Colorado, J Expo Sci Environ Epidemiol, 2022, 32, 289-294.
Mo COMPLEX− MoVI Potential Metallodrugs: Explaining the Transport and Cytotoxicity by Chemical Transformations
The transport and cytotoxicity of molybdenum-based drugs have been explained with the concept of chemical transformation, a very important idea in inorganic medicinal chemistry that is often overlooked in the interpretation of the biological activity of metal-containing systems. Two monomeric, [MoO2L1MeOH] 1 and [MoO2L2EtOH] 2, and two mixed-ligand dimeric MoVIO2 species, [{MoO2L1-2}2μ-4,4'-bipy] 3-4, were synthesized and characterized. The structures of the solid complexes were solved through SC-XRD, while their transformation in water was clarified by UV-vis, ESI-MS, and DFT. In aqueous solution, 1-4 lead to the penta-coordinated [MoO2L1-2] active species after the release of the solvent molecule 1 and 2 or removal of the 4,4'-bipy bridge 3 and 4. [MoO2L1-2] are stable in solution and react with neither serum bioligand nor cellular reductants. The binding affinity of 1-4 toward HSA and DNA were evaluated through analytical and computational methods and in both cases a non-covalent interaction is expected. Furthermore, the in vitro cytotoxicity of the complexes was also determined and flow cytometry analysis showed the apoptotic death of the cancer cells. Interestingly, μ-4,4'-bipy bridged complexes 3 and 4 were found to be more active than monomeric 1 and 2, due to the mixture of species generated, that is [MoO2L1-2] and the cytotoxic 4,4'-bipy released after their dissociation. Since in the cytosol neither the reduction of MoVI to MoV/IV takes place nor the production of reactive oxygen species ROS through Fenton-like reactions of 1-4 with H2O2 occurs, the mechanism of cytotoxicity should be attributable to the direct interaction with DNA that happens with a minor-groove binding which results in cell death through an apoptotic mechanism.
M. Mohanty, G. Sahu, A. Banerjee, S. Lima, S. A. Patra, A. Crochet, G. Sciortino, D. Sanna, V. Ugone, E. Garribba, and R. Dinda,MoVI Potential Metallodrugs: Explaining the Transport and Cytotoxicity by Chemical Transformations, Inorg Chem, 2022, 61, 4513-4532.
Associations of plasma metal levels with type 2 diabetes and the mediating effects of microRNAs
The present study aims to determine the associations of multiple plasma metal levels and plasma microRNAs (miRNAs with diabetes risk, and further explore the mediating effects of plasma miRNAs on the associations of plasma metal with diabetes risk. We detected plasma levels of 23 metals by inductively coupled plasma mass spectrometry (ICP-MS among 94 newly diagnosed and untreated diabetic cases and 94 healthy controls. The plasma miRNAs were examined by microRNA Array screening and Taqman real-time PCR validation among the same study population. The multivariate logistic regression models were employed to explore the associations of plasma metal and miRNAs levels with diabetes risk. Generalized linear regression models were utilized to investigate the relationships between plasma metal and plasma miRNAs, and mediation analysis was used to assess the mediating effects of plasma miRNAs on the relationships between plasma metals and diabetes risk. Plasma aluminum (Al, titanium (Ti, copper (Cu, zinc (Zn, selenium (Se, rubidium (Rb, strontium (Sr, barium (Ba, and Thallium (Tl levels were correlated with elevated diabetic risk while molybdenum (Mo with decreased diabetic risk (P < 0.05 after FDR multiple correction. MiR-122-5p and miR-3141 were positively associated with diabetes risk (all P < 0.05. Ti, Cu, and Zn were positively correlated with miR-122-5p (P = 0.001, 0.028 and 0.004 respectively. Ti, Cu, and Se were positively correlated with miR-3141 (P = 0.003, 0.015, and 0.031 respectively. In addition, Zn was positively correlated with miR-193b-3p (P = 0.002. Ti was negatively correlated with miR-26b-3p (P = 0.016, while Mo and miR-26b-3p were positively correlated (P = 0.042. In the mediation analysis, miR-122-5p mediated 48.0% of the association between Ti and diabetes risk. The biological mechanisms of the association are needed to be explored in further studies.
H. Nie, H. Hu, Z. Li, R. Wang, J. He, P. Li, W. Li, X. Cheng, J. An, Z. Zhang, J. Bi, J. Yao, H. Guo, X. Zhang, and M. He,Associations of plasma metal levels with type 2 diabetes and the mediating effects of microRNAs, Environ Pollut, 2022, 292, 118452.
Cross-talk Between (HydrogenSulfite and Metalloproteins: Impact on Human Health
Sulfite is a potent toxic substance causing harm to multi-organ in human. Despite toxicity, it is widely used as preservative, anti-browning and anti-oxidant in foods, beverages, and pharmaceuticals, which cause easy admission of sulfite in human. Sulfite is also produced endogenously during the catabolism of cysteine and methionine. In vivo, the serum sulfite level at physiological range is strictly maintained by a molybdenum dependent sulfite oxidase (SO, which catalyzes sulfite to sulfate via two-electron oxidation pathway. The loss of SO activity causes high serum sulfite level that fosters several diseases, including asthma, neurological dysfunction, birth defects, and heart diseases. The cytotoxicity of (bisulfite is implicated as sulfite radicals, which are generated by mainly heme-peroxidases via one-electron oxidation pathway. On the other hand, the toxic sulfite radicals are neutralized to sulfite by heme-globins. The enzymatic reduction of sulfite to sulfide is catalyzed by sulfite reductase, which contains an unusual metal cofactor, siroheme-[4Fe4S]-cluster. Overall, the interaction of sulfite with various metalloproteins in vivo is a close relation with human health. Therefore, this review describes the metabolic conversion of (bisulfite to sulfate, sulfite radical or sulfide via oxidation or reduction pathways by various metalloproteins (specially SOs, peroxidases, heme-globins, and sulfite reductases, and the potential applications of sulfite in biosensors/biofuel cells, anti-browning, and advance oxidation process.
B. K. Maiti,Cross-talk Between (HydrogenSulfite and Metalloproteins: Impact on Human Health, Chemistry- A European Journal. https://doi.org/10.1002/chem.202104342, 2022.Review
Salicylate coordination in metal-protochelin complexes
Molybdenum Mo is an essential trace element for bacteria that is utilized in myriad metalloenzymes that directly couple to the biogeochemical cycling of nitrogen, sulfur, and carbon. In particular, Mo is found in the most common nitrogenase enzyme, and the scarcity and low bioavailability of Mo in soil may be a critical factor that contributes to the limitation of nitrogen fixation in forests and agroenvironments. To overcome this scarcity, microbes produce exudates that specifically chelate scarce metals, promoting their solubilization and uptake. Here, we have determined the structure and stability constants of Mo bound by protochelin, a siderophore produced by bacteria under Mo-depleted conditions. Spectrophotometric titration spectra indicated a coordination shift from a catecholate to salicylate binding mode for Mo(VI-protochelin Mo-Proto complexes at pH < 5. pKa values obtained from analysis of titrations were 4.8 ± 0.3 for Mo(VIO2H3Proto- and 3.3 ± 0.1 for Mo(VIO2H4Proto. The occurrence of negatively charged Mo-Proto complexes at pH 6 was also confirmed by mass spectrometry. K-edge Extended X-ray absorption fine structure spectroscopy confirmed the change in Mo coordination at low pH, and structural fitting provides insights into the physical architecture of complexes at neutral and acidic pH. These findings suggest that Mo can be chelated by protochelin across a wide environmental pH range, with a coordination shift occurring at pH < 5. This chelation and associated coordination shift may impact biological availability and mineral surface retention of Mo under acidic conditions.
S. A. Doydora, O. Baars, J. M. Harrington, and O. W. Duckworth,Salicylate coordination in metal-protochelin complexes, Biometals, 2022, 35, 87-98.
Nontuberculous mycobacterial infection and environmental molybdenum in persons with cystic fibrosis: a case-control study in Colorado
RATIONALE: Nontuberculous mycobacteria (NTM) are ubiquitous environmental bacteria that may cause chronic lung disease and are one of the most difficult-to-treat infections among persons with cystic fibrosis (pwCF). Environmental factors likely contribute to increased NTM densities, with higher potential for exposure and infection. OBJECTIVE: To identify water-quality constituents that influence odds of NTM infection among pwCF in Colorado. METHODS: We conducted a population-based nested case-control study using patient data from the Colorado CF Center NTM database. We associated data from pwCF and water-quality data extracted from the Water Quality Portal to estimate odds of NTM infection. Using Bayesian generalized linear models with binomial-distributed discrete responses, we modeled three separate outcomes; any NTM infection, infections due to Mycobacterium avium complex species, and infections due to M. abscessus group species. RESULTS: We observed a consistent association with molybdenum in the source water and M. abscessus group species infection among pwCF in all models. For every 1-unit increase in the log concentration of molybdenum in surface water, the odds of infection for those with M. abscessus group species compared to those who were NTM culture-negative increased by 79%. The odds of M. abscessus group infection varied by county; the counties with the highest probability of infection are located along the major rivers. CONCLUSIONS: We have identified molybdenum in the source water as the most predictive factor of M. abscessus group infection among pwCF in Colorado. This finding will help inform patients at risk for NTM of their relative risks in residing within specific regions.
E. M. Lipner, J. L. Crooks, J. French, M. Strong, J. A. Nick, and D. R. Prevots,Nontuberculous mycobacterial infection and environmental molybdenum in persons with cystic fibrosis: a case-control study in Colorado, J Expo Sci Environ Epidemiol, 2021.
Pulmonary toxicity, genotoxicity, and carcinogenicity evaluation of molybdenum, lithium, and tungsten: A review
Molybdenum, lithium, and tungsten are constituents of many products, and exposure to these elements potentially occurs at work. Therefore it is important to determine at what levels they are toxic, and thus we set out to review their pulmonary toxicity, genotoxicity, and carcinogenicity. After pulmonary exposure, molybdenum and tungsten are increased in multiple tissues; data on the distribution of lithium are limited. Excretion of all three elements is both via faeces and urine. Molybdenum trioxide exerted pulmonary toxicity in a 2-year inhalation study in rats and mice with a lowest-observed-adverse-effect concentration (LOAEC) of 6.6 mg Mo/m(3). Lithium chloride had a LOAEC of 1.9 mg Li/m(3) after subacute inhalation in rabbits. Tungsten oxide nanoparticles resulted in a no-observed-adverse-effect concentration (NOAEC of 5 mg/m(3 after inhalation in hamsters. In another study, tungsten blue oxide had a LOAEC of 63 mg W/m(3 in rats. Concerning genotoxicity, for molybdenum, the in vivo genotoxicity after inhalation remains unknown; however, there was some evidence of carcinogenicity of molybdenum trioxide. The data on the genotoxicity of lithium are equivocal, and one carcinogenicity study was negative. Tungsten seems to have a genotoxic potential, but the data on carcinogenicity are equivocal. In conclusion, for all three elements, dose descriptors for inhalation toxicity were identified, and the potential for genotoxicity and carcinogenicity was assessed.REVIEW
N. Hadrup, J. B. Sørli, and A. K. Sharma,Pulmonary toxicity, genotoxicity, and carcinogenicity evaluation of molybdenum, lithium, and tungsten: A review, Toxicology, 2022, 467, 153098.REVIEW
Comparative outcomes of exposing human liver and kidney cell lines to tungstate and molybdate
Tungsten has no known function in humans and is a relatively new contaminant, whereas molybdenum, its congener in the periodic table, is a nutritionally essential element. In addition to early studies on molybdenosis in ruminants, their toxic effects in the form of tungstate and molybdate have been addressed primarily in rodents and are predominantly mediated by inducing oxidative stress in various tissues. The purpose of this study was to evaluate the differences between tungstate and molybdate in human liver (HepG2) and kidney (HEK293) cell lines in terms of retention in cells, effect on reactive oxygen species, and activities of xanthine oxidase and phosphatases. The cell lines were exposed to tungstate or molybdate (1 µM to 10 mM) for 24 h, lysed and analyzed for the above biochemical parameters. Despite the chemical similarity of the two anions, cell-specific differential effects were observed. At all concentrations, tungstate was retained more in HEK293 cells while molybdate was retained more in HepG2 cells. HepG2 cells were more sensitive to tungstate than molybdate, showing reduced viability at concentrations as low as 10 µM. Exposure to either anion resulted in the inhibition of protein tyrosine phosphatases at 1 mM and an increased production of reactive oxygen species (ROS) at 100 µM despite their inhibition of the ROS-producing molybdenum enzyme xanthine oxidase. In conclusion, the results indicate that excess of nutritionally essential molybdate or non-essential tungstate causes toxicity by affecting ROS- and phosphorylation-dependent signaling pathways and ensuing gene expression.
S. Sachdeva, and W. Maret,Comparative outcomes of exposing human liver and kidney cell lines to tungstate and molybdate, Toxicol Mech Methods, 2021, 1-9.
MOLYBDENUM METAL
In Vitro Degradation Behavior and Biocompatibility of Bioresorbable Molybdenum
The degradation behavior and biocompatibility of pure molybdenum (Mo) were investigated. Dissolution of powder metallurgically manufactured and commercially available Mo was investigated by ion concentration measurement after immersion in modified Kokubo's SBF (c-SBF-Ca) for 28 days at 37 degrees C and pH 7.4. Degradation layers and corrosion attack were examined with optical microscopy and REM/EDX analysis. Furthermore, potentiodynamic polarization measurements were conducted. Mo gradually dissolves in modified SBF releasing molybdate anions (MoO42-). The dissolution rate after 28 days is 10 mu m/y for both materials and dissolution accelerates over time. A non-passivating, uniform and slowly soluble degradation product layer is observed. Additionally, apoptosis and necrosis assays with Mo ion extracts and colonization tests with human endothelial (HCAEC) and smooth muscle cell lines (HCASMC) on Mo substrates were performed. No adverse effects on cell viability were observed for concentrations expected from the dissolution of implants with typical geometries and substrates were densely colonized by both cell lines. Furthermore, Mo does not trigger thrombogenic or inflammatory responses. In combination with its favorable mechanical properties and the renal excretion of bio-available molybdate ions, Mo may be an alternative to established bioresorbable metals.
C. Redlich, A. Schauer, J. Scheibler, G. Poehle, P. Barthel, A. Maennel, V. Adams, T. Weissgaerber, A. Linke, and P. Quadbeck,In Vitro Degradation Behavior and Biocompatibility of Bioresorbable Molybdenum, Metals, 2021, 11.
FETAL GROWTH
Associations between molybdenum exposure and ultrasound measures of fetal growth parameters: A pilot study
Previous studies have suggested the association of molybdenum (Mo) exposure with some adverse outcomes. However, limited epidemiological studies have been performed to explore the association between maternal Mo exposure level and fetal growth. This study recruited 220 pregnant women during their second trimester. The mother's urinary Mo concentration was measured by inductively coupled plasma mass spectrometry (ICP-MS). The fetal biometric parameters, including head circumference (HC), biparietal diameter (BPD), femur diaphysis length (FL), and abdominal circumference (AC) were assessed by prenatal ultrasound. Estimated fetal weight (EFW) was evaluated using the formula of Hadlock. Multivariable linear regression models were applied to estimate the relationships between Mo level and fetal biometric parameters, and potential confounders were adjusted. A one-unit increment in natural-logarithm transformed urinary Mo level was significantly associated with reductions in fetal AC of -0.34 cm (95%CI: -0.63, -0.04), and was negatively related to EFW (β = -18.2, 95%CI: -40.5, 4.2). Furthermore, when participants were stratified by copper (Cu) level, the results showed that the magnitude of negative association between Mo and AC (β = -0.55, 95%CI: -1.13, 0.04) was greater in pregnant women with Cu level below median value, comparing with those with Cu level above median value (β = -0.08, 95%CI: -0.57, 0.42), and a similar pattern was found for EFW, although the interaction between Mo and Cu was not significant. Our data suggested an inverse association of maternal urinary Mo level with fetal AC and EFW during the second trimester of pregnancy. These associations might be stronger in pregnant women with relatively lower Cu levels.
H. Zhao, W. Wu, X. Zhang, Q. Zhu, J. Tang, H. He, G. Chen, and J. Qin,Associations between molybdenum exposure and ultrasound measures of fetal growth parameters: A pilot study, Chemosphere, 2021, 269, 128709.
Genotoxicity and mutagenicity
Genotoxicity and mutagenicity of molybdenum(VI) and iron(III) and interactions between these microelements
Background: The aim of this study was to examine the effect of iron(III) (Fe(III)) and molybdenum(VI) (Mo(VI)) and their combinations on genotoxicity, mutagenicity, pro- and antioxidant activity in BALB/3T3 and HepG2 cells. Materials and methods: The cells were cultured in media supplemented with iron chloride or molybdenum trioxide at concentrations of 200 or 1,000 mu M. Moreover, the cells exposed to a mixture of microelements: 200 mu M of iron chloride plus 1,000 mu M of molybdenum trioxide and, in the other case, supplemented with 200 mu M of molybdenum trioxide plus 1,000 mu M of iron chloride. After 24 hours of incubation, comet, micronucleus, and Ames assays were performed. Additionally, DCFDA Cellular ROS Detection Assay, TBARS Assay, SOD Assay, Catalase Assay, and Glutathione Peroxidase Assay were performed.
Results: Additions of Fe(III) at 200 mu M plus Mo(VI) at 1,000 mu M showed synergistic effect - the increased number of comets and micronuclei in both cell lines was observed. Moreover, the number of revertants increased as well. In the case of Fe(III) at 1,000 AM plus Mo(VI) at 200 mu M, the same effect was observed. Moreover, treated cells display characteristic apoptosis in comparison to control cells. Giant and multinuclear cells were observed. In all tested microelements, the increase in number of reverse mutations was observed with and without metabolic activation. The level of reactive oxygen species and malondialdehyde (MDA) in cells increased after simultaneous exposure of cells with 200 mu M iron chloride plus 1,000 mu M molybdenum trioxide. The similar results in the case of interaction of 1,000 mu M of iron chloride plus 200 mu M of molybdenum trioxide were observed. Superoxide dismutase, catalase, and glutathione peroxidase activities decrease in a statistically significant and dose-dependent way after treatment with iron chloride and molybdenum trioxide.
Conclusion: Iron (iron(III) chloride and molybdenum (trioxide) are genotoxic and mutagenic. In our study Fe(III) and Mo(VI) show synergistic effects in genotoxicity and mutagenicity assays. Both of them can generate ROS. Moreover, Fe(III) interacts with DNA bases. These independent mechanisms can cause synergistic effects.
S. Terpilowska, and A. K. Siwicki, Genotoxicity and mutagenicity of molybdenum(VI) and iron(III) and interactions between these microelements, Trace Elements and Electrolytes, 2020, 37, 180-187.
I HAVE CORRECTED Mo(III) TO Mo(VI).
Comparative analysis of biological effects of molybdenum(IV) sulfide in the form of nano- and microparticles on human hepatoma HepG2 cells grown in 2D and 3D models
Significance of MoS2 nanoparticles as a lubricant or drug carriers indicates the need to assess their safety. In the study we analyzed the effects of MoS2 nano- and microparticles and their internalization in vitro, using 2D and 3D culture models of human hepatoma HepG2 cell line. MoS2 micro- and nanoparticles were characterized with high resolution electron microscopy (HR-SEM), X-ray diffraction (XRD) and Energy Dispersive X-Ray Spectroscopy (EDS). The cells were exposed to a range of concentrations of the nano-and microparticles suspensions (maximum of 250 mu g/mL) for 72 h. Cell viability was assessed using WST-1 reduction test and LDH release assay. Particle internalization was analyzed using scanning transmission electron microscopy (STEM). The nanoparticles were internalized into the 2D and 3D cultured cells, in spheroids more efficiently into the outer layer. For microparticles mainly particles of less than 1 mu m in diameter underwent internalization. This process, however, did not affect cell viability as measured with the WST-1 and LDH assays. STEM observation showed well preserved integrity of the cell membrane and no apparent cytotoxic effect. Although the particles seemed to be safely sequestered in vacuoles or the cytoplasm, their fate and eventual biological effects are not certain and deserve further studies.
Z. Sobanska, K. Domeradzka-Gajda, M. Szparaga, J. Grobelny, E. Tomaszewska, K. Ranoszek-Soliwoda, G. Celichowski, L. Zapor, K. Kowalczyk, and M. Stepnik,Comparative analysis of biological effects of molybdenum(IV) sulfide in the form of nano- and microparticles on human hepatoma HepG2 cells grown in 2D and 3D models, Toxicology in Vitro, 2020, 68, 104931.
PHYTOTOXICITY MoS2
The Influence of Size and Phase on the Biodegradation, Excretion, and Phytotoxicity Persistence of Single-Layer Molybdenum Disulfide
The increasing applications of single-layer molybdenum disulfide (SLMoS2) pose great potential risks associated with environmental exposure. This study found that metallic-phase SLMoS2 with a nanoscale (4N-1T-SLMoS2, ~400 nm) and microscale (M-1T-SLMoS2, ~3.6 μm) diameter at 10~25 mg/L induced significant algal growth inhibition (maximum 72.7% and 74.6%, respectively), plasmolysis, and oxidative damage, but these alterations were recoverable. Nevertheless, membrane permeability, chloroplast damage, and chlorophyll biosynthesis reduction were persistent. By contrast, the growth inhibition (maximum 55.3%) and adverse effects of nano-sized semiconductive-phase SLMoS2 (4N-2H-SLMoS2, ~400 nm) were weak and easily alleviated after 96 h of recovery. 4N-1T-SLMoS2 (0.011 μg/h) and 4N-2H-SLMoS2 (0.008 μg/h) were quickly biodegraded to soluble Mo compared with M-1T-SLMoS2 (0.004 μg/h) and excreted by algae. Incomplete biodegradation of SLMoS2 (26.8%~43.9%) did not significantly mitigate their toxicity. Proteomics and metabolomics indicated that the downregulation of proteins (50.7%~99.2%) related to antioxidants and photosynthesis and inhibition of carbon fixation and carbohydrate metabolism contributed to the persistent phytotoxicity. These findings highlight the roles and mechanisms of size and phase in the persistent phytotoxicity of SLMoS2, which has potential implications for risk assessment and environmental applications of nanomaterials.
W. Zou, X. Li, C. Li, Y. Sun, X. Zhang, C. Jin, K. Jiang, Q. Zhou, and X. Hu,The Influence of Size and Phase on the Biodegradation, Excretion, and Phytotoxicity Persistence of Single-Layer Molybdenum Disulfide,Environ. Sci. Technol. 2020, 54, 19, 12295–12306.
CYTOTOXICITY MoS2
Comparative analysis of biological effects of molybdenum(IV) sulfide in the form of nano- and microparticles on human hepatoma HepG2 cells grown in 2D and 3D models
Significance of MoS2 nanoparticles as a lubricant or drug carriers indicates the need to assess their safety. In the study we analyzed the effects of MoS2 nano- and microparticles and their internalization in vitro, using 2D and 3D culture models of human hepatoma HepG2 cell line. MoS2 micro- and nanoparticles were characterized with high resolution electron microscopy (HR-SEM), X-ray diffraction (XRD) and Energy Dispersive X-Ray Spectroscopy (EDS). The cells were exposed to a range of concentrations of the nano-and microparticles suspensions (maximum of 250 μg/mL) for 72 h. Cell viability was assessed using WST-1 reduction test and LDH release assay. Particle internalization was analyzed using scanning transmission electron microscopy (STEM). The nanoparticles were internalized into the 2D and 3D cultured cells, in spheroids more efficiently into the outer layer. For microparticles mainly particles of less than 1 μm in diameter underwent internalization. This process, however, did not affect cell viability as measured with the WST-1 and LDH assays. STEM observation showed well preserved integrity of the cell membrane and no apparent cytotoxic effect. Although the particles seemed to be safely sequestered in vacuoles or the cytoplasm, their fate and eventual biological effects are not certain and deserve further studies.
Z. Sobańska, K. Domeradzka-Gajda, M. Szparaga, J. Grobelny, E. Tomaszewska, K. Ranoszek-Soliwoda, G. Celichowski, L. Zapór, K. Kowalczyk, and M. Stępnik,Comparative analysis of biological effects of molybdenum(IV) sulfide in the form of nano- and microparticles on human hepatoma HepG2 cells grown in 2D and 3D models, Toxicol In Vitro, 2020, 68, 104931.
Cytotoxicity Elicited by Molybdenum Disulphide in Different Size of Particles in Human Airway Cells
The present investigation was aimed to study the cytotoxic response induced by molybdenum disulfide in nano- (MoS2-NPs) and micro- (MoS2-MPs) size of particle in human bronchial (BEAS-2B) and alveolar (A549) cells. The cells were exposed with different particle size of MoS2 in concentrations range 1-200 mu g/mL for 24, 48, and 72 h, and then the cytotoxicity assays (MTT and NRU) was performed. Afterwards, long-term toxicity was assessed by colony forming efficiency assay (CFEA) during 10 days exposure of the cells. Both MoS2-NPs and MoS2-MPs showed similar, weak cytotoxic effects on BEAS-2B and A549 cells assessed by MTT assay, that is reduction of cell viability to approx. 60-70% at concentrations of 2.5 and 5 mu g/mL. The percentage viability remained relatively constant at this level across all concentrations above 5 mu g/mL. In long-term exposure, both MoS2 inhibited colony formation in a wider range of concentrations to 200 mu g/mL. MoS2-NPs were slightly more cytotoxic than MoS2-MPs. The data suggest the low potential hazardous nature of both MoS2 tested with an indication of higher toxicity of MoS2-NPs.
L. Zapor,Cytotoxicity Elicited by Molybdenum Disulphide in Different Size of Particles in Human Airway Cells, Rocznik Ochrona Srodowiska, 2019, 21, 794-809.
CANCER
Environmental etiology of gastric cancer in Iran: a systematic review focusing on drinking water, soil, food, radiation, and geographical conditions
The aim of this systematic review study was to investigate the causal relationship between environmental factors and gastric cancer (GC) in Iran. In a narrow definition, the environment includes water, soil, air, and food. This definition was the main criterion for the inclusion of articles in this study. In addition, exposure to radiation and geographical conditions were considered as less investigated environmental factors in the literatures. International (PubMed, Web of Science, ScienceDirect, Scopus, and Cochran) and national (Scientific Information Database) databases were searched for articles on GC and environmental risk factors in Iran. Twenty-six articles were found to meet the inclusion criteria after title, abstract, and full text review. Risk factors identified for GC include consumption of red meat; high fat, fried, and salted meat; smoked, salted, and fried foods; some dairy products; roasted and fried seeds; strong and hot tea; and un-piped and unchlorinated drinking water, as well as exposure to radiation, loess sediment, soft and grassy soil, soil containing low concentration of molybdenum , and proximity to volcanos. Fresh fruits and vegetable, fresh fish, and honey consumption were recognized as protective agents. Given the risk factors identified, strategies to prevent GC would be educating people to choose a healthy diet and to cook and store food properly, providing access to safe drinking water, taking into account topographical and geographical conditions in choosing a right location to build residential areas, and regulating the use of radiation-emitting devices.
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H. R. Ghaffari, M. Yunesian, R. Nabizadeh, S. Nasseri, A. Sadjadi, F. Pourfarzi, H. Poustchi, and A. Eshraghian,Environmental etiology of gastric cancer in Iran: a systematic review focusing on drinking water, soil, food, radiation, and geographical conditions, Environmental science and pollution research international, 2019 26:10487–10495 https://doi.org/10.1007/s11356-019-04493-8
CANCER
Serum Trace Elements and Their Associations with Breast Cancer Subgroups in Korean Breast Cancer Patients
The relationships between serum levels of trace elements and breast cancer remain relatively unknown. In this study, we investigate serum levels of seven trace elements in Korean breast cancer patients compared to controls without breast cancer. Serum trace element levels were determined using inductively coupled plasma mass spectrometry in Korean breast cancer patients before initiation of breast cancer treatment. Korean females without breast cancer served as a control group. Trace element levels were measured in the discovery cohort (n = 287) and were validated in an independent cohort (n = 142). We further investigated possible associations between trace element levels and the presence of lymph node metastasis, distant metastasis, or triple-negative breast cancer among breast cancer patients in subgroup analyses. Serum manganese and molybdenum levels were significantly higher (p < 0.05) in breast cancer patients than in controls. Serum copper levels were significantly higher in breast cancer patients with distant metastasis, while selenium levels were significantly lower. Other trace elements were neither significantly different between breast cancer patients and controls nor between subgroups of breast cancer patients. Our study provides insights about the potential roles and impacts of trace elements through an assessment of the associations between trace elements and breast cancer.
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R. Choi, M. J. Kim, I. Sohn, S. Kim, I. Kim, J. M. Ryu, H. J. Choi, J. M. Kim, S. K. Lee, J. Yu, S. W. Kim, S. J. Nam, J. E. Lee, and S. Y. Lee,Serum Trace Elements and Their Associations with Breast Cancer Subgroups in Korean Breast Cancer Patients, Nutrients, 2019, 11(1), 37; https://doi.org/10.3390/nu11010037
Toxicology of Molybdenum - Humans
DIABETES
Oxidative DNA damage mediates the association between urinary metals and prevalence of type 2 diabetes mellitus in Chinese adults
Previous publications have indicated that some metals are associated with an increased prevalence of type 2 diabetes mellitus (T2DM); however, the mechanisms remain largely unknown. This study aimed to quantify the associations of oxidative DNA damage with urinary metals and prevalence of T2DM among the general population, and further to assess the role of oxidative DNA damage in mediating the association of urinary metals with prevalence of T2DM. Diagnoses of T2DM were performed clinically or by measuring fasting levels of plasma glucose >= 7.0 mmol/L. Concentrations of urinary metals and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in 2127 participants were measured using inductively coupled plasma-mass spectrometry and high-performance liquid chromatography. Relationships among urinary metals, 8-OHdG (a biomarker for oxidative DNA damage), and prevalence of T2DM were analyzed using mediation analysis. After adjusting for covariates, we found that the log-transformed levels of urinary copper, arsenic, selenium, molybdenum, and antimony were positively associated with prevalence of T2DM. Urinary 8-OHdG was not only positively correlated with copper, arsenic, selenium, and antimony in an upwardly trending, dose-responsive manner but was also positively associated with prevalence of T2DM (odds ratio (OR): 1.95; 95% CI: 1.17-3.24). Mediation analysis estimated that urinary 8-OHdG mediated 13.22% and 8.84% of associations between prevalence of T2DM and concentrations of urinary arsenic and antimony, respectively (all P value < 0.05). Our findings suggested that urinary arsenic and antimony concentrations were associated with an increased prevalence of T2DM by a mechanism partly involving oxidative DNA damage. (C) 2018 Elsevier B.V. All rights reserved.
L. L. Xiao, Y. Zhou, J. X. Ma, W. W. Sun, L. M. Cao, B. Wang, C. M. Zhu, S. J. Yang, D. M. Wang, J. Yuan, and W. H. Chen,Oxidative DNA damage mediates the association between urinary metals and prevalence of type 2 diabetes mellitus in Chinese adults, Science of the Total Environment, 2018, 627, 1327-1333.
Systemic sclerosis and exposure to heavy metals: A case control study of 100 patients and 300 controls
Objective: This case control study assessed: 1) the relationship of systemic sclerosis (SSc) related to exposure to heavy metals; and 2) the risk of SSc related to occupational exposure in male and female patients.
Methods: From 2005 to 2008, 100 patients with a definite diagnosis of SSc were included in the study; 3 age, gender, and smoking habit matched controls were selected for each patient. All SSc patients and controls underwent detection and quantification of heavy metal traces in hair samples, using multi-element inductively coupled plasma mass spectrometry (ICP-MS).
Results: SSc patients exhibited higher median levels of the following metals: antimony (p = 0.001), cadmium (p = 0.0003), lead (p = 0.02), mercury (p = 0.02), molybdenum (p = 0.04), palladium (p < 0.0001) and zinc (p = 0.0003). A marked association between SSc and occupational exposure was further found for: 1) antimony (p = 0.008) and platinum (p = 0:04) in male patients; and 2) antimony (p = 0.02), cadmium (p = 0.001), lead (p = 0.03), mercury (p = 0.03), palladium (p = 0.0003) and zinc (p = 0.0001) in female patients
Conclusion: The results show the impact of occupational risk factors in the development of SSc for: antimony, cadmium, lead, mercury, molybdenum, palladium and zinc. Thus, occupational exposure should be systematically checked in all SSc patients at diagnosis. Finally, the association between SSc and occupational exposure may be variable according to patients' gender. (C) 2017 Elsevier B.V. All rights reserved.
I. Marie, J. F. Gehanno, M. Bubenheim, A. B. Duval-Modeste, P. Joly, S. Dominique, P. Bravard, D. Noel, A. F. Cailleux, J. Benichou, H. Levesque, and J. P. Goulle,Systemic sclerosis and exposure to heavy metals: A case control study of 100 patients and 300 controls, Autoimmunity Reviews, 2017, 16, 223-230.
[Systemic scleroderma, also called diffusescleroderma or systemic sclerosis, is an autoimmune disease of the connective tissue. It is characterized by thickening of the skin caused by accumulation of collagen, and by injuries to small arteries. https://en.wikipedia.org/wiki/Systemic_scleroderma.
Scleroderma is caused by the immune system attacking the connective tissue under the skin and around internal organs and blood vessels. This causes scarring and thickening of the tissue in these areas.
There are two main types of scleroderma: localised scleroderma – just affects the skin systemic sclerosis – may affect blood circulation and internal organs as well as the skin.
https://www.nhs.uk/conditions/scleroderma/]
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Chronic kidney disease
High prevalence of elevated molybdenum levels in pediatric CKD patients. A cross-sectional and longitudinal study
AIMS: Many of the secondary effects of high levels of molybdenum (Mo) overlap with symptoms commonly seen in pediatric patients with chronic kidney disease (CKD).
We measured plasma Mo levels and examined the relationship between Mo levels and kidney function.
MATERIALS AND METHODS: The study was carried out at the London Health Sciences Centre in London, Ontario, Canada with 36 children and adolescents 4 - 18 years of age with CKD. There were 1 - 6 trace element measurements (Mo and copper (Cu)) per patient. We studied the proportion of patients with abnormal trace element levels and the relationship between trace element levels and estimated glomerular filtration rate (eGFR), calculated using the Filler formula. Plasma Mo and Cu levels were measured using High Resolution Sector Field Inductively Coupled Mass Spectrometry. Anthropomorphic data and blood parameters were collected from our electronic chart program.
RESULTS: Median eGFR was 51 mL/min/1.73m2 (35, 75). Median Mo level was 2.00 microg/L (1.40, 2.88). 20 patients had at least one set of Mo levels above the published reference interval in either unit, and the results of 46% of the tests were above the interval. There was a strong negative correlation between the Mo levels and the eGFR (Spearman's r = -0.627, p. < 0.0001).
CONCLUSIONS: Our study suggests that pediatric patients with CKD have elevated plasma levels of Mo, which may cause secondary effects commonly associated with CKD. The elevated Mo levels in our center's catchment area may cause an accumulation of this trace element in patients with impaired renal function.
Yang, G., Belostotsky, V., Kobrzynski, M., Huang, S. S., and Yang, L.,High prevalence of elevated molybdenum levels in pediatric CKD patients. A cross-sectional and longitudinal study, Clinical nephrology, 2017 88 79-85
NHS Choices: http://www.nhs.uk/Conditions/Kidney-disease-chronic/Pages/Diagnosis.aspx
The main test for kidney disease is a blood test that's used to work out how well your kidneys are working. The test measures the levels of a waste product called creatinine in your blood. Using this result, a calculation that takes into account your age, gender and ethnic group is then done to work out how many millilitres of waste your kidneys are able to filter in a minute.This measurement is known as your estimated glomerular filtration rate (eGFR).Healthy kidneys should be able to filter more than 90ml/min. You may have kidney disease if your result is lower than this.