Urinary Excretion Of Metals Research Articles

Association between metal exposure and oxidative stress in preschool children and the moderating role of urinary creatinine

The association between childhood metal exposure and oxidative stress levels is of paramount importance, as children are a susceptible group to metal toxicity and elevated oxidative damage has been linked to a variety of diseases. Despite the fact that urinary creatinine is commonly used to account for variations in urine dilution, it may introduce analytical bias if creatinine excretion is influenced by the same factors that affect urinary metal excretion or if metal exposure compromises kidney function. In this study, we evaluated the individual and joint association between urinary metal ion concentrations and the oxidative stress biomarker 8-hydroxy-2′ -deoxyguanosine in preschool children and assessed the moderation role of urinary creatinine. Multiple linear regression showed that copper and selenium were negatively correlated with 8-hydroxy-2′ -deoxyguanosine, arsenic and antimony were positively correlated with 8-hydroxy-2′ -deoxyguanosine. Restricted cubic spline demonstrated the non-linear relationship between lithium, nickel, arsenic, tin, and antimony and 8-hydroxy-2′ -deoxyguanosine. Bayesian kernel machine regression and quantile g-computation analyses showed a positive association between urinary metal ion concentration and 8-hydroxy-2′ -deoxyguanosine levels, with selenium being the most significant metal ion contributing to elevated oxidative stress levels. Moderation analyses revealed that the association between urinary metal ions and 8-hydroxy-2′ -deoxyguanosine is more significant at high urinary creatinine levels. The results indicated the importance of adequately accounting for urinary creatinine levels to avoid overestimation of metal exposure and distortion of the true association between metal exposure and oxidative damage.

Effects of work schedule and period of exposure on changes in urinary chromium and nickel excretion among rotating shift workers in a stainless-steel plant

ABSTRACTWe investigated the association between the period of exposure and changes in urinary excretion of chromium and nickel among rotating shift workers in a stainless-steel plant. The study participants were composed of two groups: the workers who were occupationally exposed to metals (“exposed group”) and those who were not occupationally exposed to metals (“unexposed group”). The exposed and unexposed groups consisted of 56 and 40 male rotating shift workers, respectively. Urine samples were collected immediately before and immediately after the day shift, evening shift, and night shift. Urinary chromium and nickel were measured using inductively coupled plasma mass spectrometry. To correct for variations in urine dilution, urinary metal concentrations were expressed as a ratio to urinary creatinine concentration. In the exposed group, post-shift urinary excretion of chromium was significantly higher than pre-shift excretion. However, although urinary chromium excretion clearly increased after the day and night shift [63% (p < .0001) and 87% (p < .0001), respectively], urinary chromium excretion after the evening shift was only slightly higher than that measured before the evening shift (8%, p = .028). Similar patterns were found for urinary nickel excretion (p = .0001, 0.20, and 0.18 for the day, evening, and night shifts, respectively). Non-uniform urinary excretion of metals between the day shift, evening shift, and night shift were observed in the exposed group; specifically, urinary metal excretion increased only slightly during the evening shift. In the unexposed group, no significant increase or decrease was found in median urinary chromium or nickel excretion (p= .63–0.87). Work shift-specific permissible exposure level would be necessary.

Associations of renal function with urinary excretion of metals: Evidence from NHANES 2003–2012

BackgroundUrinary metals are considered measures of long-term exposures of metals, such as cadmium (Cd). Some studies indicate reduced renal function may affect the urinary excretion of several metals in general population making assessments difficult. ObjectivesTo examine whether reduced renal function is associated with reduced urinary excretion of 12 metals or their metabolites and, in turn, an underestimated measure of Cd in general population. MethodsWe conducted analyses using data from the National Health and Nutrition Examination Survey (NHANES) 2003–2012. Multiple linear regression models were used to examine the associations between urinary metal levels and estimated glomerular filtration rate (eGFR). Restricted cubic spline regression models were used to evaluate the nonlinearity. ResultsUrinary metal levels significantly increased (p < 0.001) with increasing eGFR, except for antimony (p = 0.172). Urinary levels of arsenic, dimethylarsonic acid, cobalt, molybdenum and tungsten increased linearly with eGFR, while Cd, lead, mercury, barium, cesium and thallium increased nonlinearly (p < 0.001) with eGFR. Based on a restricted cubic spline regression model, we found, corresponding to a fixed blood Cd adverse cutpoint of 5 μg/L, predicted urinary Cd cutpoints substantially varied from 0.78–1.21 μg/g for urinary Cd between those aged <40 years and who had chronic kidney disease and those aged 60 years or over with normal renal function, respectively. ConclusionReduced renal function is associated with reduced urinary metals; and associations are also observed across the eGFR range not just in the reduced range. Urinary abnormal cutpoints of metals are likely dependent on eGFR and age. The associations between urinary exposure of metals and disease risk are likely underestimated without considering the modifying effect of renal function.

Preeclampsia and toxic metals: a case-control study in Kinshasa, DR Congo.

BackgroundPreeclampsia is frequent in Kinshasa (Democratic Republic of Congo), especially during the dry season. We tested whether preeclampsia was associated with exposure to environmental metals.MethodsUsing a case-control design, 88 women hospitalized with preeclampsia (cases) and 88 healthy pregnant women from the antenatal clinic (controls) were included in the study; 67 and 109 women were enrolled during the rainy and dry season, respectively. The concentrations of 24 elements were quantified by inductively coupled plasma mass spectrometry (ICP-MS) in 24-h urine collections. Differences in the urinary excretion of metals were investigated between cases and controls, and the interaction with season was assessed.ResultsCases and controls were well matched regarding age, parity and duration of pregnancy. In controls, the urinary concentrations of most elements were substantially higher than reference values for adults from industrially developed countries, e.g. for lead: geometric mean (GM) 8.0 μg/L [25th-75th percentile 3.1–13.8]. The daily urinary excretions of 14 metals were significantly higher in women with preeclampsia than in control women, e.g. for lead: GM 61 μg/day (25th–75th percentile 8–345) in women with preeclampsia vs 9 μg/day (25th–75th percentile 3–21) in controls (p < 0 · 001). A significant interaction was found between season and preeclampsia for several elements, with higher urinary excretions in preeclamptic women than controls during the dry season, but not during the rainy season.ConclusionsThis study revealed not only that women with preeclampsia excrete higher amounts of several toxic metals, especially lead, than control women, but also that this excretion exhibits seasonal variation, thus possibly explaining the high incidence and seasonal variation of preeclampsia in Kinshasa. Although the exact sources of this exposure are unknown, these findings underscore the need for preventing environmental exposures to lead and other toxic metals.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-016-0132-1) contains supplementary material, which is available to authorized users.

Assessment of cytogenetic damage in lymphocytes and in exfoliated nasal cells of dental laboratory technicians exposed to chromium, cobalt, and nickel

Dental laboratory technicians may be exposed to metal alloys that are used in the production of crowns, bridges and removable partial dentures. These alloys consist of 35–65% cobalt, 20–30% chromium, 0–30% nickel, and small amounts of molybdenum, silica, beryllium, boron and carbon. The aim of this study was to assess whether dental technicians are occupationally exposed to chromium, cobalt and nickel, by analyzing urinary excretion levels of these metals and to investigate the genotoxic effects of occupational exposure associated with dental prostheses production operations by analyzing cytokinesis-blocked micronucleus (CB-MN) frequencies in peripheral lymphocytes and micronucleus (MN) frequencies in exfoliated nasal cells from 27 dental laboratory technicians and 15 control subjects. The differences in the urinary excretion of metals between technicians and controls were statistically significant. The mean (±S.D.) CB-MN frequencies (‰) in peripheral lymphocytes were 4.00 (±2.98) among the dental technicians and 1.40 (±1.30) among the controls, a statistically significant difference ( P<0.005). The mean (±S.D.) MN frequencies (‰) in nasal cells were 3.50 (±1.80) among the dental technicians and 1.19 (±0.53) among the controls, which was also a statistically significant difference ( P<0.005). There was a significant correlation between duration of exposure and MN frequencies in lymphocytes ( r=0.642, P<0.01), but not in nasal cells of technicians. Our data reveal that in vivo exposure to chromium, nickel and cobalt metals is evident and that this occupational exposure may contribute to the observed genotoxic damage in two types of cells, e.g. lymphocytes and exfoliated nasal cells. However, it cannot be determined which compound(s) are responsible for the genotoxic damage observed in this study.

Identification of a mechanism by which the methylmercury antidotes N-acetylcysteine and dimercaptopropanesulfonate enhance urinary metal excretion: transport by the renal organic anion transporter-1.

N-Acetylcysteine (NAC) and dimercaptopropanesulfonate (DMPS) are sulfhydryl-containing compounds that produce a dramatic acceleration of urinary methylmercury (MeHg) excretion in poisoned animals, but the molecular mechanism for this effect is unknown. NAC and DMPS are themselves excreted in urine in high concentrations. The present study tested the hypothesis that the complexes formed between MeHg and these anionic chelating agents are transported from blood into proximal tubule cells by the basolateral membrane organic anion transporters (Oat) 1 and Oat3. Xenopus laevis oocytes expressing rat Oat1 showed increased uptake of [(14)C]MeHg when complexed with either NAC or DMPS but not when complexed with L-cysteine, glutathione, dimercaptosuccinate, penicillamine, or gamma-glutamylcysteine. In contrast, none of these MeHg complexes were transported by Oat3-expressing oocytes. The apparent K(m) values for Oat1-mediated transport were 31 +/- 2 microM for MeHg-NAC and 9 +/- 2 microM for MeHg-DMPS, indicating that these are relatively high-affinity substrates. Oat1-mediated uptake of [(14)C]MeHg-NAC and [(14)C]MeHg-DMPS was inhibited by prototypical substrates for Oat1, including p-aminohippurate (PAH), and was trans-stimulated when oocytes were preloaded with 2 mM glutarate but not glutamate. Conversely, efflux of [(3)H]PAH from Oat1-expressing oocytes was trans-stimulated by glutarate, PAH, NAC, DMPS, MeHg-NAC, MeHg-DMPS, and a mercapturic acid, indicating that these are transported solutes. [(3)H]PAH uptake was competitively inhibited by NAC (K(i) of 2.0 +/- 0.3 mM) and DMPS (K(i) of 0.10 +/- 0.02 mM), providing further evidence that these chelating agents are substrates for Oat1. These results indicate that the MeHg antidotes NAC and DMPS and their mercaptide complexes are transported by Oat1 but are comparatively poor substrates for Oat3. This is the first molecular identification of a transport mechanism by which these antidotes may enhance urinary excretion of toxic metals.

Nephrotoxicity of simultaneous exposure to mercury and uranium in comparison to individual effects of these metals in rats.

Both inorganic mercury and uranium are known nephrotoxicants in mammals. In this study, the renal toxicity of a concurrent exposure to inorganic mercury and uranium was compared with the nephrotoxic effects of the individual metals in a rat model. Eight groups of rats, 10 animals per group, were subcutaneously given a single administration of mercuric chloride (HgCl2, 0.34 mg/kg and 0.68 mg/kg), uranyl acetate dihydrate (UAD, 2.5 mg/kg and 5 mg/kg), or combinations of both compounds at the same doses. A ninth group of rats received sc injections of 0.9% saline and was designated as the control group. Necrosis of proximal tubules, which was observed in all experimental groups, was the most relevant morphologic abnormality. Marked changes, which were remarkably greater than those induced by the individual elements, were noted in some urinary parameters in the groups concurrently exposed to HgCl2 and UAD. It could be an indicator of a synergistic interaction between mercury and uranium. In contrast, compared with the urinary levels found after individual administration of the highest doses of mercury and uranium, significant reductions in the urinary concentrations of these elements were noted following simultaneous exposure to both metals. At these doses, the reduction in the urinary metal excretion was also accompanied by significant decreases in the renal content of mercury and uranium. Whereas the results of some parameters pointed out a possible synergistic interaction between mercury and uranium, other measures hinted that an antagonistic interaction between these elements is also present.

Urinary excretion of essential metals following intravenous calcium disodium edetate: an estimate of free zinc and zinc status in man

Ethylenediaminetetraacetic acid (EDTA) is a powerful metal chelating agent used in the treatment of lead poisoning. EDTA also binds strongly to other metals. Thus, following intravenous infusion of CaNa 2EDTA in healthy subjects the urinary excretion of calcium, copper, iron, magnesium and zinc were assessed. CaNa 2EDTA significantly increased the urinary excretion of all metals except magnesium with greatest increases for iron (×3.8 above baseline) and zinc (×22). In addition, an in vitro dialysis study with a simplified serum showed that zinc (4.1×10 −3 μmol/h) was taken up more rapidly than iron (2.9×10 −3 μmol/h) by EDTA. The degree of binding of iron and zinc by EDTA depends on two factors: namely, the affinity of EDTA for Zn 2+ and Fe 3+, and the levels of unbound hydrated Zn 2+ and Fe 3+ (`free' ions). Despite differences in the rate of chelation of Zn 2+ and Fe 3+ by EDTA we show that the measurements of (a) circulating free iron, from routine clinical measurements of transferrin bound iron, and (b) the ratio of zinc:iron excreted in urine could provide an estimate of circulating free zinc, and thereby of zinc status, in man. In addition, EDTA treatment should be evaluated for patients with iron overload.

Increased sister chromatid exchanges and tumor markers in workers exposed to elemental chromium-, cobalt- and nickel-containing dusts

Sister-chromatid exchange (SCE) in blood lymphocytes, serum tumors markers, carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA), and urinary excretion of chromium, cobalt and nickel were determined in 26 male workers occupationally exposed to chromium, cobalt and nickel dust and in 25 controls matched for age and smoking habits. The differences in the urinary excretion of metals between exposed persons and controls were statistically significant. An analysis of variance on the SCE rank values revealed that both exposure status (exposed persons vs. controls) and smoking habits (smokers and former smokers vs. never smokers) had a statistically significant effect. For the tumor markers, the analysis of variance did not reveal a statistically significant difference between exposed persons and controls. However, CEA serum levels were significantly correlated not only with smoking habits but also with duration of exposure. As cobalt is only weakly mutagenic, these results suggest that the small amount of absorbed chromium and nickel may have been sufficient to induce SCE. The hypothesis that tumor markers may be increased in groups of subjects exposed to genotoxic substances deserves further study.

Biliary and urinary excretion of metals in humans.

Fifteen metals (lead, cadmium, arsenic, inorganic mercury, organic mercury, iron, manganese, magnesium, chromium, zinc, copper, nickel, cobalt, tin, and aluminum) were determined in the hepatic bile and urine collected simultaneously from three Japanese individuals (2 males, 1 female). The presence of these metals was classified as follows: hepatic biliary concentrations were higher than urinary concentrations (lead, arsenic, and iron); urinary concentrations were higher than hepatic biliary concentrations (cadmium, inorganic mercury, tin, cobalt, magnesium, chromium, copper, zinc, and nickel); hepatic biliary concentrations were almost equal to urinary concentrations (manganese and organic mercury); and relationship between hepatic biliary and urinary concentrations changed occasionally (aluminum). Eight essential metals (iron, manganese, magnesium, zinc, chromium, copper, nickel, and cobalt) were detected at considerable concentrations in hepatic bile. Accounting for the daily flow volume of hepatic bile and the reabsorption of these metals, the supplementation of these metals should occur during treatment of diseases accompanied by loss of hepatic bile.

Mobilisation of heavy metals into the urine by CaEDTA: relation to erythrocyte and plasma concentrations and exposure indicators.

To investigate the effects of calcium disodium ethylenediamine tetra-acetate (CaEDTA) on the urinary excretion, erythrocyte, and plasma concentrations and exposure indicators of seven heavy metals, CaEDTA was administered by intravenous infusion to 20 workers exposed to lead, zinc, and copper. The workers' blood lead concentrations ranged from 22 to 59 micrograms/dl (mean 38 micrograms/dl (1.8 mumol/l]. The 24 hour urinary excretion of metals after CaEDTA administration (mobilisation yield) was on average 13 times the background excretion for lead, 11 times for zinc, 3.8 times for manganese, 3.4 times for cadmium, 1.3 times for copper, and 1.1 times for chromium; no significant increase was found for mercury. The mobilisation yield of lead (MPb) was significantly correlated with whole blood and erythrocyte concentrations and the urinary excretion of lead but not with its plasma concentration; similarly, the mobilisation yield of cadmium was significantly correlated with its erythrocyte concentration. In addition, MPb was significantly correlated with intra-erythrocytic enzyme delta-aminolaevulinic acid dehydratase activity and urinary coproporphyrin excretion. The relation between the mobilisation yield of heavy metals and their body burden (and toxic signs) is discussed in the light of these findings.

The effects of CaEDTA injection on lead, zinc, copper and ALAD in erythrocyte, plasma and urine in lead-exposed workers: a 24-h observation.

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the concentrations of lead, zinc and copper in plasma, erythrocyte and urine, and the delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocyte, we administered CaEDTA in 1-h intravenous infusion to ten male gun metal founders with blood-lead concentration of 39 to 64 micrograms/dl (mean 49 micrograms/dl). We found that the plasma concentration of lead, following a rapid rise within the first 3 h, fell temporarily to the level significantly lower than the initial level 19 h after start of the infusion. The plasma concentration of zinc fell to the minimal level 5 h after the infusion; and the erythrocyte concentration of zinc and the ALAD activity concurrently rose to the maximal level 5 h after the infusion. By contrast, no significant alteration was observed in the concentrations of copper in plasma and erythrocyte. The maximal level of urinary metal excretion was attained during the period between 1 and 2 h after start of CaEDTA infusion for lead; within 2 h for zinc; and between 2 and 4 h for copper. The urinary metal excretion returned to the initial level 14 to 24 h after infusion for zinc and copper; but lead excretion was still higher than the initial level during this period. The difference in the kinetics of the three metals following CaEDTA injection is discussed in the light of these findings.

Studies of Urinary Excretion of Metals in Welders Using Cadmium-Silver Solder

Studies of Urinary Excretion of Metals in Welders Using Cadmium-Silver Solder

Circadian rhythms in the urinary excretion of metals and organic substances in "healthy" men.

Circadian rhythms in the urinary excretion of metals and organic substances were examined in ten "healthy" men under conditions of water loading and restriction. Four characteristic rhythms were observed: (1) decreased excretion during the night for lead and urinary flow rate; (2) decreased excretion of hippuric acid, delta-aminolevulinic acid, coproporphyrin, creatinine, and total urinary solutes during the night and morning hours; (3) increased excretion of mercury and zinc during the morning hours; and (4) no significant variation for copper. Excretion of lead, hippuric acid, delta-aminolevulinic acid, and total urinary solutes was significantly correlated with urinary flow rate and creatinine excretion, which suggested that their circadian rhythms were the consequence of reduced glomerular filtration and increased reabsorption by the distal tubule and collecting duct during the night and morning hours. Similarly, it was suggested that the mercury and zinc rhythms resulted partly from increased reabsorption during the night hours; the coproporphyrin rhythm reflected reduced glomerular filtration of coproporphyrinogen during the night and morning hours.

Influence of chronic MnCl2 and EDTA treatment on tissue levels and urinary excretion of trace metals in rats.

Rats were chronically exposed interperitoneally to Mn as MnCl2-4H2O for 30 days. Treatment was then discontinued and the urinary excretion of metals (Mn, Zn, Fe, Cu) with or without EDTA treatment was monitored. Kidney, testes, brain, and muscle, but not liver, revealed elevated Mn levels due to chronic exposure to the metal alone. In brain, the tegmentum, and striatum accumulated more Mn than the hippocampus. EDTA-treated rats excreted 12x as much Mn/day in urine as those not treated with EDTA; Zn excretion was increased 6x, Fe 2x, and Cu decreased 0.2x. EDTA administration enhanced the natural elimination of excess Mn from skeletal muscle, but not from the other examined tissues. Changes were also observed in the concentrations of other trace metals. Mn treatment was accompanied by decreased hepatic Fe levels, increased Cu levels in the testes and the corpus striatum and hippocampus of the brain, and an increase in Zn, Fe, and Cu in skeletal muscle. Except for the elevated brain Cu, these effects were reversible if Mn treatment was discontinued. A highly significant positive correlation was noted between the urinary excretion of Mn and Fe under the influence of EDTA treatment.

Observations on urinary and fecal excretion of heavy metals (Cd, Pb and Zn) in the patients of the so-called “Itai Itai” disese

In order to make clear the cause of the so-called “Itai Itai” disease, we measured the amonut of heavy metals (Cd, Pb and Zn) in the urine and faeces of the patients as well as healthy men. The results obtained were as follows:1. The urinary cadmium excretion of the patients in the hospital was found markedly in greater quantity than their contrasts (in cases of other bone diseasesr sufferers and healthy men).2. The urinary metal excretion (Cd, Pb and Zn) of the patients and healthy men in the epidemic district was compared with that of healthy men in the contrasted district, where such a case has been never seen till now. The most marked difference was the greater cadmium excretion by the former. And in the epidemic district, the considerable amount of cadmium was found in the urine of the patients and healthy men alike.3. The cadminm content of rice and soybean in the epidemic district was clearly greater than in the contrasted district. With lead and zinc there was not so clear a difference as with cadmium.