Mercury Concentrations In Plasma Research Articles

Characterization of pathological changes in the olfactory system of mice exposed to methylmercury

Methylmercury (MeHg) is a well-known environmental neurotoxicant that causes severe brain disorders such as Minamata disease. Although some patients with Minamata disease develop olfactory dysfunction, the underlying pathomechanism is largely unknown. We examined the effects of MeHg on the olfactory system using a model of MeHg poisoning in which mice were administered 30 ppm MeHg in drinking water for 8 weeks. Mice exposed to MeHg displayed significant mercury accumulation in the olfactory pathway, including the nasal mucosa, olfactory bulb, and olfactory cortex. The olfactory epithelium was partially atrophied, and olfactory sensory neurons were diminished. The olfactory bulb exhibited an increase in apoptotic cells, hypertrophic astrocytes, and amoeboid microglia, mainly in the granular cell layer. Neuronal cell death was observed in the olfactory cortex, particularly in the ventral tenia tecta. Neuronal cell death was also remarkable in higher-order areas such as the orbitofrontal cortex. Correlation analysis showed that neuronal loss in the olfactory cortex was strongly correlated with the plasma mercury concentration. Our results indicate that MeHg is an olfactory toxicant that damages the central regions involved in odor perception. The model described herein is useful for analyzing the mechanisms and treatments of olfactory dysfunction in MeHg-intoxicated patients.

Toxicokinetics of methylmercury in diabetic KK-Ay mice and C57BL/6 mice.

We compared the toxicokinetics of methylmercury (MeHg) in KK-Ay type 2 diabetic mice and C57BL/6J mice to evaluate how metabolic changes associated with diabetes affect MeHg toxicokinetics. A single dose of MeHg (0.2, 1, or 5 mg mercury/kg) was administered orally to 12-week-old KK-Ay and C57BL/6J male mice. Total mercury concentrations in plasma, blood cells, whole blood, and tissues (brain, kidneys, liver, and pancreas) were measured after 4, 7, 11, and 14 days. The volume of distribution/bioavailability and the elimination rate constant per day were higher in KK-Ay mice, while the terminal elimination half-life was lower in almost all samples of KK-Ay mice. The area under the curve was lower in all blood and almost all tissue samples from KK-Ay mice. Total clearance/bioavailability was lower in all blood and tissue samples of KK-Ay mice at all MeHg doses. These results indicate that MeHg is more rapidly absorbed by, and eliminated from, the blood cells, brain, liver, kidney, and pancreas of KK-Ay mice under the experimental conditions. Different patterns of tissue-to-plasma and tissue-to-whole blood partition coefficients suggest that notable differences in MeHg transfer between plasma and blood cells affect its distribution in tissues of the two mouse strains. These findings are useful to understand the selective distribution of MeHg to target organs and the sensitivity to MeHg in pathological states.

Concentrations of Trace Elements in Hemodialysis Patients: A Prospective Cohort Study

Low concentrations and excessive concentrations of trace elements have been commonly reported in hemodialysis patients, but available studies have several important limitations. Random sample of patients drawn from a prospective cohort. 198 incident hemodialysis patients treated in 3 Canadian centers. We used mass spectrometry to measure plasma concentrations of the 25 elements at baseline, 6 months, 1 year, and 2 years following enrollment in the cohort. We focused on low concentrations of zinc, selenium, and manganese and excessive concentrations of lead, arsenic, and mercury; low and excessive concentrations of the other 19 trace elements were treated as exploratory analyses. Low and excessive concentrations were based on the 5th and 95th percentile plasma concentrations from healthy reference populations. At all 4 occasions, low zinc, selenium, and manganese concentrations were uncommon in study participants (≤5.1%,≤1.8%, and≤0.9% for zinc, selenium, and manganese, respectively) and a substantial proportion of participants had concentrations that exceeded the 95th percentile (≥65.2%,≥74.2%, and≥19.7%, respectively). Almost all participants had plasma lead concentrations above the 95th percentile at all time points. The proportion of participants with plasma arsenic concentrations exceeding the 95th percentile was relatively constant over time (9.1%-9.8%); the proportion with plasma mercury concentrations that exceeded the 95th percentile varied between 15.2% and 29.3%. Low arsenic, platinum, tungsten, and beryllium concentrations were common (>50%), as were excessive cobalt, manganese, zinc, vanadium, cadmium, selenium, barium, antimony, nickel, molybdenum, lead, and chromium concentrations. There was no evidence that low zinc, selenium, or manganese concentrations exist in most contemporary Canadian hemodialysis patients. Some patients have excessive plasma arsenic and mercury concentrations, and excessive lead concentrations were common. These findings require further investigation.

Direct Absorption of Methyl Mercury by Lymph

Methyl mercury is contained in fish and seafood products and is taken up into the body in food. While the central nervous system is known as a target organ, methyl mercury also induces autoimmunity and acts as a potent immunosuppressor. The aim of the present study is to know whether methyl mercury is directly absorbed by lymph. Conscious rats were infused with methyl mercury (4 mg/kg) via duodenal tubing as a single pulse infusion, followed by the continuous infusion of saline, and lymphatic fluids were continuously collected from the thoracic lymph duct every 30 min until 360 min after infusion. Mercury was detected immediately after infusion, and total mercury contents in lymph gradually increased until 90-120 min, remained steady, and then gradually decreased until 360 min; however, the amount of mercury collected during 330-360 min was about twofold higher than during 0-30 min. The amount of cumulative mercury in lymph at 360 min was 1.4 μg. In contrast, blood mercury concentration was 2.4 μg/ml 5 min after infusion, with the value at 360 min being 12.6 times higher than at 5 min. Plasma mercury concentration was 56 ng/ml at 5 min, with hundreds of nanograms per milliliter of mercury detected until 360 min. From the present study, it is concluded that some methyl mercury is directly absorbed by lymph and remains steady 6 h after infusion.

Metal Concentrations in Plasma and Cerebrospinal Fluid in Patients with Alzheimer’s Disease

Background/Aims: The homeostasis of essential metals such as copper, iron, selenium and zinc may be altered in the brain of subjects with Alzheimer’s disease (AD). Methods: Concentrations of metals (magnesium, calcium, vanadium, manganese, iron, cobalt, nickel, copper, zinc, selenium, rubidium, strontium, molybdenum, cadmium, tin, antimony, cesium, mercury and lead) were determined in plasma and cerebrospinal fluid (CSF) by inductively coupled plasma mass spectrometry in 173 patients with AD and in 87 patients with the combination of AD and minor vascular components (AD + vasc). Comparison was made with 54 healthy controls. Results: The plasma concentrations of manganese and total mercury were significantly higher in subjects with AD (p < 0.001) and AD + vasc (p ≤ 0.013) than in controls. In CSF, however, the concentrations of vanadium, manganese, rubidium, antimony, cesium and lead were significantly lower among subjects with AD (p ≤ 0.010) and AD + vasc (p ≤ 0.047) than in controls. Strong positive correlations were noted between plasma Cs versus CSF Cs in subjects with AD (r_s = 0.50; p < 0.001), and AD + vasc (r_s = 0.68; p < 0.001). Conclusion: Besides the raised plasma mercury concentrations, no consistent metal pattern in plasma or CSF was observed in patients with AD.

Blood mercury levels of dental students and dentists at a dental school.

To determine the blood mercury levels in dental students and clinical teaching staff in a dental school using amalgam as a restorative material. A dental school in Ege University, Turkey surveyed during one academic year. Cross-sectional study of groups of dental students (n=92) in years I to V, clinical teachers in restorative dentistry (n=16) and controls (n=14). Mercury concentration was estimated in venous blood samples using a cold vapour atomic absorption method at the commencement and end of the academic year. Daily air mercury levels were determined in clinical and teaching areas by measuring the darkening of palladium chloride discs using spectrophotometry. There were statistically significant increases (p<0.001) in plasma mercury concentration between measurements in all groups at the end of the academic year. Red cell mercury levels were also consistently elevated. Although the highest levels of mercury were recorded in persons working with amalgam, increased levels were also found in subjects working in the teaching classrooms but not with amalgam (controls and first year students). Increased mercury levels appeared to be due to background exposure from spillage of mercury and amalgam residues on floors. Increased mercury hygiene and regular control of working atmosphere should be implemented to prevent mercury exposure in the dental pre-clinical laboratory.

Mercury vapour exposure: a study of dental student

Objective To determine the blood mercury levels in dental students and clinical teaching staff in a dental school using amalgam as a restorative material. Setting A dental school in Ege University, Turkey surveyed during one academic year. Subjects and methods Cross-sectional study of groups of dental students (n=92) in years I to V, clinical teachers in restorative dentistry (n=16) and controls (n=14). Mercury concentration was estimated in venous blood samples using a cold vapour atomic absorption method at the commencement and end of the academic year. Daily air mercury levels were determined in clinical and teaching areas by measuring the darkening of palladium chloride discs using spectrophotometry. Results here were statistically significant increases (p<0.001) in plasma mercury concentration between measurements in all groups at the end of the academic year. Red cell mercury levels were also consistently elevated. Although the highest levels of mercury were recorded in persons working with amalgam, increased levels were also found in subjects working in the teaching classrooms but not with amalgam (controls and first year students). Conclusion Increased mercury levels appeared to be due to background exposure from spillage of mercury and amalgam residues on floors. Increased mercury hygiene and regular control of working atmosphere should be implemented to prevent mercury exposure in the dental pre-clinical laboratory.

Lactational Exposure and Neonatal Kinetics of Methylmercury and Inorganic Mercury in Mice

The concentration of mercury in milk and the distribution pattern in the sucking pup was followed over time after administration of a single iv injection of 0.5 mg/kg body wt of203Hg-labeled methylmercuric chloride or mercuric chloride to lactating mice on Day 10 of lactation. Mercury concentrations in milk of the dams and in whole body, blood, plasma, GI-tract, liver, kidneys, and brain of the offspring were followed up to 11 days after dosing (until lactational Day 21). Following the inorganic mercury dose to the dams, most of the mercury in milk was delivered to the pups during the first 24 h, but the maximum mercury concentration in plasma and tissues of pups was not reached until 7 days after dosing, indicating a prolonged absorption of inorganic mercury in the sucking pup. Pups of dams given methylmercury were exposed to a much lower and constant mercury concentration in milk. The estimated accumulated mercury dose via milk per pup of dams given methylmercury was less than half of that estimated after the inorganic mercury dose. When the accumulated dose via milk from methylmercury-exposed dams was compared to the amount of mercury in pup's carcass (whole body minus GI-tract including content), it was revealed that almost all mercury delivered via milk was absorbed, and that the suckling pups had a very low elimination of mercury until lactational Day 17. Lactational exposure following a maternal methylmercury or inorganic mercury dose resulted in almost similar mercury concentrations in liver, kidneys, and plasma of the suckling, but higher concentrations in brain (as most 14 times) and also twice as high mercury body burden in the methylmercury group. Thus, differences in kinetics indicate that lactational exposure of methylmercury is a greater hazard for the breast-fed infant than inorganic mercury.

No evidence of renal toxicity from amalgam fillings.

Dental amalgam continuously releases mercury. Studies of sheep [Boyd et al., Am. J. Physiol. 261 (Regulatory Integrative Comp. Physiol. 30): R1010-R1014, 1991] showed decreased renal function after placement of amalgam fillings. In this study, renal function was investigated in 10 healthy volunteers before and after amalgam removal. The subjects had an average of 18 tooth surfaces filled with amalgam, which was removed during one dental session. One week before and sixty days after removal, the glomerular filtration rate (GFR) was determined by 51Cr-EDTA clearance technique. Blood and urine samples were collected for analysis of mercury, creatinine, beta 2-microglobulin, N-acetyl-beta-glucosaminidase (NAG), and albumin 1 wk before and 1, 2, and 60 days after amalgam removal. The plasma mercury concentration increased significantly 1 day after removal. Sixty days later, significantly lower mercury levels were found in blood, plasma, and urine. The GFR values were similar before and after mercury exposure (mean 94 and 94 ml/min per 1.73 m2, respectively). No detectable effects occurred on excretion of NAG, beta 2-microglobulin, or albumin. It is concluded that no signs of renal toxicity could be found in conjunction with mercury released from amalgam fillings.

Long-term use of nicotine chewing gum and mercury exposure from dental amalgam fillings.

In experimental studies, chewing gum has been shown to increase the release rate of mercury vapor from dental amalgam fillings. The aim of the present study was to investigate the influence of long-term frequent chewing on mercury levels in plasma and urine. Mercury levels in plasma (P-Hg) and urine (U-Hg), and urinary cotinine were examined in 18 subjects who regularly used nicotine chewing gum, and in 19 referents. Age and number of amalgam surfaces were similar in the two groups. Total mercury concentrations in plasma and urine were determined by means of cold vapor atomic absorption spectrometry. Urinary cotinine was determined by gas chromatography-mass spectrometry. The chewers had been using 10 (median) pieces of gum per day for the past 27 (median) months. P-Hg and U-Hg levels were significantly higher in the chewers (27 nmol/L and 6.5 nmol/mmol creatinine) than in the referents (4.9 nmol/L and 1.2 nmol/mmol creatinine). In both groups, significant correlations were found between P-Hg or U-Hg on the one hand and the number of amalgam surfaces on the other. In the chewers, no correlations were found between P-Hg or U-Hg and chewing time per day or cotinine in urine. Cotinine in urine increased with the number of pieces of chewing gum used. The impact of excessive chewing on mercury levels was considerable.

Immune factors, dental amalgam, and low-dose exposure to mercury in Swedish adolescents.

Occupational high-dose exposure to metallic mercury can cause immune disturbances in sensitive individuals. Whether low-dose exposure to inorganic mercury from dental amalgam has this effect in humans is one of the issues related to the concept of oral galvanism and is supported by results of animal studies. This study explored some cellular immune factors (B- and T-lymphocytes, T4, T8, monocytes, neutrophilic, eosinophilic, and basophilic granulocytes, and large unstained cells) and some humoral immune factors (immunoglobulins IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE, albumin, alfa-1-antitrypsin, orosomucoid, haptoglobin, and antinuclear antibodies) in 41 healthy 15-y-old schoolchildren. The relationship between these factors and amalgam fillings and mercury concentrations in plasma (P-Hg) were investigated. A low, but significant correlation (r = 0.40, p < .05) was found between the number of amalgam surfaces and the P-Hg values, which were low for both sexes (median value = 1.8 nmol/l). There was no significant influence of the number of amalgam surfaces or P-Hg on the immune factors tested, except random findings. The girls had significantly higher values of T8, IgG, and IgG1 than the boys.

Exposure to mercury via breast milk in suckling offspring of maternal guinea pigs exposed to mercury vapor after parturition.

Exposure to an exogenous chemical via milk causes superimposition on the body burden that might have already existed in the neonatal organism due to in utero exposure. Such exposure via breast milk is avoidable, although transplacental exposure cannot be avoided at present. In this paper, mercury exposure via breast milk was examined in an animal model. Maternal guinea pigs were shortly exposed to mercury vapor at the mean concentrations of 6-10 mg/m3 immediately after parturition. Newborn guinea pigs were then nursed by the natural mothers. Mercury concentrations in breast milk and tissue samples were determined on d 3, 5, and 10 postpartum. Mercury concentrations in breast milk were slightly lower than plasma mercury concentrations of the maternal guinea pigs over the observation period. However, the decrease in the mercury concentration in breast milk with time was slower than that in maternal plasma. Mercury concentrations in major organs of the neonates were highest in kidney, followed by liver and lung. In brain and whole blood, mercury concentrations were slightly elevated compared with the nonexposed control. Organ distribution of mercury in the suckling neonates indicated that they were exposed via breast milk to inorganic, not elemental, mercury.

Effect of amino acids on brain uptake of methyl mercury

To investigate the effect of amino acids on the brain uptake of methyl mercury (MM), methyl mercury chloride (MMC), and some amino acids were injected iv to Wistar strain male rats (190 ± 10 g). One hour after the simultaneous injection of 10 μmol and 100 μmol l-cysteine ( l-Cys) to the rat, brain mercury content increased about three times as compared with that after a single injection of MMC alone. This effect of l-Cys was depressed by pre- and post-treatment with l-phenylalanine ( l-Phe), but not with l-lysine ( l-Lys) or l-glutamic acid ( l-Glu). BAL also increased the brain uptake of MM. However, l-Phe did not exert an effect on the increased brain uptake of MM. When 10 μmol MMC was injected to the rat treated with l-Phe or l-isoleucine ( l-Ile) (pre-, simultaneous, and post-treatment), brain mercury 2 hr after the injection was lower than that after the single injection of MMC. At that time, there was no significant difference in blood and plasma mercury concentrations between the l-Phe-treated and nontreated rats. Treatment with l-Lys and l-Glu did not affect the brain mercury content after MMC injection. Brain mercury after the injection of 10 μmol MMC increased with time. The rate of increase was lowered by pre-, simultaneous, and post-treatment with l-Phe for 2, 6, 9, and 12 hr. When l-Phe injection was started 12 hr after MMC injection and continued repeatedly for 12 hr, the brain mercury content was low when compared with that after the single injection of MMC. These data demonstrate that the brain uptake of MM is depressed by l-Phe and l-Ile, which are neutral amino acids, and not by l-Lys and l-Glu, which are a basic and an acidic amino acid, respectively.

Effects of l- or d-cysteine coadministration on short-term distribution of inorganic mercury in the rat

Male Sprague-Dawley rats received iv injections of mercuric chloride alone or in combination with l-cysteine or d-cysteine. Mercury concentrations in kidney, liver, and cerebrum 5 min after injection increased linearly over the dose range of 0.1, 0.5, 1.0, and 2.0 μmol of mercury/kg. Over this dose range, coadministration of l-cysteine or d-cysteine at a 2-to-1 molar ratio relative to mercury increased renal mercury concentrations and reduced mercury accumulation in the liver, cerebrum, and erythrocytes. Renal mercury concentrations were highly correlated with plasma mercury concentrations 5 min after injection and coadministration of l-cysteine or d-cysteine did not alter this relationship. Hepatic and cerebral mercury concentrations were also highly correlated with plasma mercury concentrations but coadministration of either thiol compound altered the relationship between plasma and tissue mercury concentrations. These data suggested that different processes underlie short-term mercury accumulation in different tissues. Investigations of the effects on tissue distribution of various molar ratios of l- or d-cysteine relative to mercury further suggested that direct complexation of mercury by either thiol may be a critical factor in the control of mercury deposition in these tissues.

Inorganic and organic mercury in blood, urine and hair in low level mercury vapour exposure.

Fourteen Japanese females exposed to elemantal mercury vapour of concentration; 0.001–0.019 mg Hg/m3, were examined for inorganic and organic mercury concentrations in red blood cells, plasma, urine, and hair. Examinations were conducted the times; at 0,4 and 8 months of mercury exposure. No significant change of inorganic and organic mercury in urine was observed for three examinations. Both inorganic and organic mercury in plasma, and only organic mercury in red blood cells, increased significantly after commencement of mercury work. The hair organic mercury values stayed constant. The intake of organic mercury was judged as constant from the constancy of hair mercury values, and the change of organic mercury concentrations in plasma and red blood cells must have been elicited from the intake of elemental mercury. The reason why the increase of plasma mercury values did not reflect to urine mercury values was discussed.