Sexual differences in the excretion of organic and inorganic mercury by methyl mercury-treated rats

Adult male and female Long Evans rats received 1 mumole of methyl (203Hg) mercuric chloride per kilogram sc. Whole-body retention of mercury and excretion of organic and inorganic mercury in urine and feces were monitored for 98 days after dosing. Females cleared mercury from the body more rapidly than did males. The major route of mercury excretion was feces. By 98 days after dosing, cumulative mercury excretion in feces accounted for about 51% of the dose in males and about 54% of the dose in females. For both sexes, about 33% of the dose was excreted in feces as inorganic mercury. Cumulative excretion of organic mercury in feces accounted for about 18 and 21% of the dose in males and females, respectively. Urinary excretion of mercury was quantitatively a smaller route for mercury clearance but important sexual differences in loss by this route were found. Over the 98-day experimental period, males excreted in urine about 3.2% of the dose and females excreted 7.5%. Cumulative organic Hg excretion in urine accounted for 1.8% of the dose in males and 5.3% of the dose in females. These sexual differences in urinary and fecal excretion of organic and inorganic mercury following methyl mercury treatment were consistent with previous reports of sexual differences in mercury distribution and retention in methyl mercury-treated rats, particularly sexual differences in organic mercury uptake and retention in the kidney. Relationships between body burdens of organic or inorganic Hg and output of these forms of Hg in urine and feces were also found to be influenced by the interval after MeHg treatment and by sex. Relationship between concentration of Hg in liver and feces and in kidney and urine differed for organic and inorganic Hg and depended upon sexual status and interval after MeHg treatment. These findings emphasize that sexual differences in distribution, retention, and metabolism of methyl mercury are factors to be considered in estimations of hazards associated with exposure to this agent.     

Distribution and excretion of some mercury compounds after long term exposure

Summary The investigation has shown that the first three members of the homologeous series of alkyl mercury salts are most likely stable in the body of the experimental animals as regards the bond between the metal and the organic radical. Different salts of such compounds lose however their individuality by hydrolysis. It appears therefore to be without prospects to find an alkyl mercury salt, which is excreted appreciably faster than other alkyl mercury salts. There are some differences in the way of distribution of the three alkyl-derivatives between different organs. These differences are however small.Since all the investigated alkyl mercury compounds are resorbed to about the same extent, the administered amounts being about the same, there are probably no appreciable differences between the rate of excretion between them.There is no reason to belive that the alkyl compounds have a certain affinity to the brain.The methoxyethyl mercury also seems to be stable in the body of the experiment animals. The mercury(II)ion and the phenyl mercury ion appear to be subjected to a rather slow chemical change.The chemical change is accompanied by a translocation of the reaction products towards the kidneys. This may be the result of a change of the partition coefficients.A simple excretion mechanism is assumed for the alkyl mercury salts, according to which the excretion per unit time is proportional to the simultaneous mercury concentration in the body. The excretion data are in good agreement with this mechanism. The excretion data for methoxyethyl mercury hydroxide are also in rather good agreement with this mechanism. The data of phenyl mercury hydroxide and mercury(II) nitrate do not accord with this simple theory, since it appears that these compounds are changed during the experiment.The biological half-life of the methyl mercury salts is indicated to between 15 and 20 days and of methoxyethyl mercury hydroxide to be between 4 and 10 days. For the unstable compounds mercury(II) nitrate and phenyl mercury hydroxide the half-life is of course more difficult to obtain. The excretion data indicate a half-life of between 4 and 10 days in the beginning of the experiment.This work has been supported by AB Casco, Stockholm, Sweden.     

Excretion of methyl mercury in human feces

Fecal excretion of methyl mercury was confirmed in four Japanese male subjects. Perhaps the methyl mercury detected in feces is dependent on (a) the unabsorbed methyl mercury in diet, (b) exfoliation of intestinal cells, (c) hepatic bile, and (d) intestinal methylation of inorganic mercury. The calculated amounts of methyl mercury excreted daily in feces were similar to those found in urine.     

Measurement of urinary mercury excretion by atomic absorption in health and disease

Taylor, A., and Marks, V. (1973).British Journal of Industrial Medicine,30, 293-296. Measurement of urinary excretion by atomic absorption in health and disease. Excretion of mercury was measured by a cold-vapour atomic absorption technique on samples of urine from five groups of people having varying exposure to mercury.

Serial investigations of up to 14 days were carried out on eight subjects to determine the temporal relationship between exposure and excretion.

Subjects with no exposure excreted 0-10 μg mercury per gramme creatinine. Similar values were found in laboratory staff and men assembling hollow cathode lamps. Excretion of mercury by dental workers was significantly increased. No correlation between exposure and excretion of mercury was seen in the subjects investigated.

The significance of measuring urinary excretion in the detection of mercury intoxication is discussed. The suggestion is made that urinary mercury excretion of more than 20 μg/g creatinine or 40 μg mercury per 24 hours should be considered evidence of recent or remote exposure to mercury. It is concluded that measurement of urinary mercury excretion is important in revealing those persons who may ultimately develop symptoms of toxicity.

     

牛磺酸对汞致肾细胞凋亡的影响

目的探讨牛磺酸对汞致肾细胞凋亡的影响。方法昆明种小鼠24只随机分成3组，第1组为阴性对照组，第2组为单纯染汞组，第3组为牛磺酸干预组。单纯染汞组小鼠腹腔注射3．0mg／kg的氯化汞溶液，对照组注射0．9％的氯化钠溶液，注射容量为0．2ml／10g。牛磺酸干预组于注射3．0mg／kg的HgCl2前2h腹腔注射4mmol／kg牛磺酸溶液。24h后将小鼠颈椎错位处死，制备透射电镜标本，观察凋亡细胞形态；免疫组化法检测bcl-2和bax凋亡相关基因表达。制备单细胞悬液，流式细胞仪进行凋亡细胞百分数分析。结果透射电镜观察，对照组小鼠肾近曲小管细胞形态规则，单纯染汞组表现微绒毛排列紊乱，染色质聚集成块，核破碎释放出凋亡小体。凋亡小体被邻近细胞吞噬等典型细胞凋亡形态。牛磺酸组显示接近正常的肾小管上皮细胞的形态，仅见到少量的线粒体嵴溶解。流式细胞仪分析染汞组明显高于对照组，牛磺酸干预组均显著低于染汞组。免疫组化检测牛磺酸干预组bcl-2蛋白的表达显著高于染汞组；bax蛋白的表达显著低于染汞组。结论牛磺酸可以抵抗汞所致的肾细胞凋亡，使凋亡相关基因bcl-2的表达上调。bax的表达下调。     

Urinary excretion of mercury after occupational exposure to mercury vapour and influence of the chelating agent meso-2,3-dimercaptosuccinic acid (DMSA).

The spontaneous and chelator mediated excretion of mercury in urine was investigated in male subjects occupationally exposed to mercury vapour (alkaline battery and chloralkali plants) who did not exhibit any sign of kidney damage. The time course of the spontaneous elimination of mercury in urine was examined in seven workers (age 22-40) who had been removed from exposure to mercury vapour (average duration of exposure 4.4 years) because their urinary mercury concentrations repeatedly exceeded 100 micrograms/g creatinine. The post exposure observation period started 10 to 29 days after the date of removal and lasted about 300 days (slow HgU elimination phase). For each worker, the kinetics of the spontaneous HgU decline followed a first order process; the biological half life ranged from 69 to 109 days (mean 90 days). The increased urinary excretion of mercury after a single oral administration of 2 g meso-2,3-dimercaptosuccinic acid (DMSA) was investigated in 16 control workers (group A; age 23 to 49), in 11 workers removed from exposure for at least two years (group B; age 27 to 41), and in 16 workers currently exposed to mercury vapour (group C; age 21 to 58). In group C, the DMSA experiment was repeated twice (three weeks before and three weeks after a holiday) after measures had been taken to reduce the mercury emission. The urinary mercury excretion was significantly higher during the 24 hours after DMSA administration in all groups compared with that in the 24 hours before. The bulk (50-70%) of the DMSA stimulated mercury excretion appeared within the first eight hours. In each group, the amount of mercury (microgram Hg/24h) excreted after DMSA was significantly correlated with that before administration of DMSA. The groups whose exposure had ceased, however, exhibited much higher correlation for coefficients (r=0.97 for group B and 0.86 for group C after three weeks of holiday) than those currently exposed to mercury vapour (r-0.66 for group C before and 9.58 after reduction of exposure). The data suggest that after a few days of cessation of occupational exposure to mercury vapour the HgU before and after administration of DMSA mainly reflects the amount of mercury stored in the kidney, which represents a mercury pool with a slow turnover.     

Urinary excretion of mercury after occupational exposure to mercury vapour and influence of the chelating agent meso-2,3-dimercaptosuccinic acid (DMSA).

The spontaneous and chelator mediated excretion of mercury in urine was investigated in male subjects occupationally exposed to mercury vapour (alkaline battery and chloralkali plants) who did not exhibit any sign of kidney damage. The time course of the spontaneous elimination of mercury in urine was examined in seven workers (age 22-40) who had been removed from exposure to mercury vapour (average duration of exposure 4.4 years) because their urinary mercury concentrations repeatedly exceeded 100 micrograms/g creatinine. The post exposure observation period started 10 to 29 days after the date of removal and lasted about 300 days (slow HgU elimination phase). For each worker, the kinetics of the spontaneous HgU decline followed a first order process; the biological half life ranged from 69 to 109 days (mean 90 days). The increased urinary excretion of mercury after a single oral administration of 2 g meso-2,3-dimercaptosuccinic acid (DMSA) was investigated in 16 control workers (group A; age 23 to 49), in 11 workers removed from exposure for at least two years (group B; age 27 to 41), and in 16 workers currently exposed to mercury vapour (group C; age 21 to 58). In group C, the DMSA experiment was repeated twice (three weeks before and three weeks after a holiday) after measures had been taken to reduce the mercury emission. The urinary mercury excretion was significantly higher during the 24 hours after DMSA administration in all groups compared with that in the 24 hours before. The bulk (50-70%) of the DMSA stimulated mercury excretion appeared within the first eight hours. In each group, the amount of mercury (microgram Hg/24h) excreted after DMSA was significantly correlated with that before administration of DMSA. The groups whose exposure had ceased, however, exhibited much higher correlation for coefficients (r=0.97 for group B and 0.86 for group C after three weeks of holiday) than those currently exposed to mercury vapour (r-0.66 for group C before and 9.58 after reduction of exposure). The data suggest that after a few days of cessation of occupational exposure to mercury vapour the HgU before and after administration of DMSA mainly reflects the amount of mercury stored in the kidney, which represents a mercury pool with a slow turnover.     

Mobilized mercury in subjects with varying exposure to elemental mercury vapour

Summary In a mercury mobilization test, 0.3 g of the complexing agent sodium 2,3-dimercaptopropane-1-sulfonate (DMPS) was given orally to 10 workers with moderate occupational exposure to elemental mercury vapour, controls, and to 5 referents without amalgam fillings. In the workers, DMPS caused an increase in 24-h urinary mercury excretion by a factor of 10; in the dentists, 5.9; in the controls, 5.3; and in the amalgam-free referents, 3.8. Of the mercury excreted during 24 h, 59% appeared during the first 6 h. Close, albeit non-linear, associations were found between mobilized mercury and the premobilization mercury levels in plasma and urine, but not with the duration of occupational exposure or the rough estimate of the integrated function of blood levels vs. time. The present data indicate that mercury mobilized after a single DMPS dose in close connection with exposure is mainly an index of recent exposure and is not significantly affected by slow body pools or long-term exposure.     

N-acetylcysteine as an antidote in methylmercury poisoning.

Methylmercury is a ubiquitous environmental pollutant and potent neurotoxin. Treatment of methylmercury poisoning relies almost exclusively on the use of chelating agents to accelerate excretion of the metal. The present study demonstrates that oral administration of N-acetylcysteine (NAC), a widely available and largely nontoxic amino acid derivative, produces a profound acceleration of urinary methylmercury excretion in mice. Mice that received NAC in the drinking water (10 mg/ml) starting at 48 hr after methylmercury administration excreted from 47 to 54% of the 203Hg in urine over the subsequent 48 hr, as compared to 4-10% excretion in control animals. When NAC-containing water was given from the time of methylmercury administration, it was even more effective at enhancing urinary methylmercury excretion and at lowering tissue mercury levels. In contrast, excretion of inorganic mercury was not affected by oral NAC administration. The ability of NAC to enhance methylmercury excretion when given orally, its relatively low toxicity, and is wide availability in the clinical setting indicate that it may be an ideal therapeutic agent for use in methylmercury poisoning.     

People with high mercury uptake from their own dental amalgam fillings.

OBJECTIVES--To describe people with high mercury (Hg) uptake from their amalgam fillings, and to estimate the possible fraction of the occupationally unexposed Swedish population with high excretion of urinary Hg. METHODS--Three case reports are presented. The distribution of excretion of urinary Hg in the general population was examined in pooled data from several sources. RESULTS--The three cases excreted 23-60 micrograms of Hg/day (25-54 micrograms/g creatinine), indicating daily uptake of Hg as high as 100 micrograms. Blood Hg was 12-23 micrograms/l, which is five to 10 times the average in the general population. No other sources of exposure were found, and removal of the amalgam fillings resulted in normal Hg concentrations. Chewing gum and bruxism were the probable reasons for the increased Hg uptake. Extrapolations from data on urinary Hg in the general population indicate that the number of people with urinary excretion of > or = 50 micrograms/g creatinine could in fact be larger than the number of workers with equivalent exposure from occupational sources. CONCLUSION--Although the average daily Hg uptake from dental amalgam fillings is low, there is a considerable variation between people; certain people have a high mercury uptake from their amalgam fillings.     

汞作业工人尿蛋白的凝胶色谱和十二烷基磺酸钠...

The results showed that in mankind, the urinary mercury consisted mainly of low molecular mercury complex (LM-Hg), low molecular protein-combining mercury (LMW-Pr-Hg) and high or middle molecular protein-combining mercury (HMMW-Pr-Hg) just like that found in animal experiments. The study demonstrated that the LM-Hg seemed to be helpful in refleting the detoxifying potentiality of renal tubular cell to wards mercury. The HMMW-Pr-Hg, made up mainly by albumin-combining mercury, was also a chief component of urinary mercury and showed parallel changes with the level of total urinary mercury. It suggested that the filtration through glomerulus was also an important source of urinary mercury, thus offering a new and completely different mercury excretion mechanism of kidney from classical conception. The results showed as well that the constitution of urinary protein in mercury workers might be of great variety, but the typical figure was the low molecular pattern. Because the changes in constitution of urinary protein were earlier than the changes in quantity, it was considered that the component analysis of urinary protein would be a more significant subclinical index.     

Evaluation of the chelating action of methicillin in prolonged experimental metallic mercury poisoning.

Studies were conducted to measure the effect of methicillin on the urinary excretion of mercury in rabbits poisoned for three months by mercury vapour. Simultaneously, studies were done to compare the quantity of eliminated mercury after treatment with methicillin or penicillamine (Cuprenil). The results show that the urinary excretion of mercury in animals treated with either drug was clearly greater than in untreated controls. Furthermore, the quantity of eliminated mercury after treatment with methicillin was significantly greater than after treatment with penicillamine.     

Evaluation of the chelating action of methicillin in prolonged experimental metallic mercury poisoning

Studies were conducted to measure the effect of methicillin on the urinary excretion of mercury in rabbits poisoned for three months by mercury vapour. Simultaneously, studies were done to compare the quantity of eliminated mercury after treatment with methicillin or penicillamine (Cuprenil). The results show that the urinary excretion of mercury in animals treated with either drug was clearly greater than in untreated controls. Furthermore, the quantity of eliminated mercury after treatment with methicillin was significantly greater than after treatment with penicillamine.     

Uptake of mercury by the hair of methylmercury-treated newborn mice

Human hair has unique advantages in monitoring environmental exposures to methylmercury. Using newborn Balb/c mice as a model system, the incorporation of methylmercury into the hair was studied and compared with methylmercury distributions in other tissues. Newborn mice were given intraperitoneal injections of 203Hg-labeled methylmercury at designated times according to hair growth stages of the mouse. Animals were sacrificed 2 days after dosing. Distribution of mercury in pelt and other tissues was measured. The level of mercury in pelt was found to correlate with hair growth. The amount of mercury in pelt peaked when hair growth was most rapid and the total amount of mercury in pelt was significantly higher than that in other tissues, constituting 40% of the whole body burden. However, when the hair ceased growing, the amount of mercury in pelt dramatically dropped to 4% of whole body burden and mercury concentrations in other tissues except brain were elevated. Autoradiographic studies with tritium-labeled methylmercury demonstrated that methylmercury concentrated in hair follicles in the skin. Within hair follicles and hairs, methylmercury accumulated in regions that are rich in high-sulfur proteins. The uptake of inorganic mercury (administered as HgCl2) by pelt was also compared with that of methylmercury. The amount of inorganic mercury found in pelt was less than one-half that of methylmercury in animals with growing hair. Cessation of hair growth did not decrease the inorganic mercury level in pelt to the same extent as in the case of methylmercury.     

Nephrotoxic actions of low-dose mercury in mice: protection by zinc

The authors conducted this study to determine if very-low-dose (i.e., 4 ppm) mercury is nephrotoxic and, if so, whether the nephrotoxic actions of mercury in mice could be prevented by zinc intake. Animals were administered 4 ppm mercuric chloride and/or 800 ppm zinc chloride in their drinking water for 12 wk. The animals were sacrificed at the end of the exposure period, and their kidneys were excised, weighed, and processed for histological study. Both metals reduced significantly (p < .05) the absolute and relative kidney weights of the animals. Zinc-treated animals showed normal kidney histology that was comparable with that of the control. Mercury treatment produced necrosis and widening of the glomeruli, whereas a combination of both metals resulted in protection from the toxic effects, with most nephrons resembling the control. The results indicate that low-dose mercury exposure in mice kidney induces some degenerative effects, which are prevented by zinc.     

Mobilization of mercury by DMPS in occupationally exposed workers and in model experiments on rats: evaluation of body burden

The aim of the study was to evaluate the efficacy of DMPS (sodium-2,3-dimercapto-1-propane sulfonate) (Dimaval) administration for mobilizing mercury from the body in occupationally exposed people and experimental animals. Two doses of DMPS were administered at a 24-h interval to: (a) groups of people occupationally exposed to merkury--workers of the chloralkali industry (n = 43), and dentists (n = 12), (b) non-exposed individuals (n = 20), and (c) rats chronically exposed to mercury vapour at the concentration of 0.8 mg/m3 Hg degree (6 h/day, 5 days/week) for 15 weeks. In an out-patient mobilizing test, the urinary excretion of mercury 48 h after the administration of the first dose reached 1513 micrograms in the group of industrial workers, 132.6 micrograms in dentists, and 3.78 micrograms in controls. In rats, two consecutive doses of DMPS decreased kidney content of mercury by about 30% and 50% after oral and intraperitoneal administration, respectively. Kidney mercury burden was calculated on the basis of the data from animal and human studies of the mobilization of mercury via urine after DMPS treatment: 61, 2800 and 28,000 ng/g in controls, dentists and workers, respectively. It was estimated that two doses of DMPS mobilized 17-20% (after oral administration) and 25-30% (after intramuscular administration) of kidney mercury burden, both in the control and exposed subjects.     

Change in the iso-enzyme profiles of urinary N-acetyl-beta-D-glucosoaminidase in workers exposed to mercury

The iso-enzyme profiles of urinary N-acetyl-beta-D-glucosoaminidase (NAG) were studied in the workers from a chloro-alkaline electrolysis plant that had been continuously exposed to elemental mercury. The same workers then had a work break of four months and were later re-exposed to mercury for another five months. The activities of urinary NAG in workers exposed to mercury before and after the work break and in the control group were 2.09 +/- 1.03 IU/L; 0.90 +/- 0.52 IU/L and 1.13 +/- 0.35 IU/L, respectively. The fraction of the dominant A form activity in the total activity, in the workers exposed to mercury after a work break (85.31 +/- 5.32%), was almost equal to the fraction of A in the control group (84.64 +/- 2.75%). The percent fraction of A forms (A and A2) during continuous exposure was almost equal to the sum of the fractions A and A2 in the control group and for exposure after the work break. The fraction of the B form activity in the total activity during exposure to elemental mercury for five months after the work break (7.41 +/- 3.45%) was lower (P < 0.1) than the fraction of the B form in the control group (8.62 +/- 2.19%). The decrease in the fraction of the B form compared with the control group was more significant (P < 0.001) in the case of continuously exposed workers (5.25 +/- 2.55%). Beside the major A and B iso-enzymes of NAG, the A2 form was also isolated, and its fraction in the control group (6.73 +/- 2.15%) was not negligible. For workers exposed to mercury for five months, it was 7.28 +/- 3.52%. It is concluded that mercury affected the increased exocytosis of iso-enzyme A and the inhibition of B iso-enzyme of NAG. The increase in activity of urinary NAG in subjects exposed to mercury was a consequence of the increased excretion of A form. It was established also that the four months work break was sufficient for the repair of renal damages that occurred during continuous exposure, and which were monitored by the activity of NAG. Thus, the effects of mercury seem to have been reversible.     

Ratio of organs to blood of mercury during its uptake by normal and acatalasemic mice

The brain/blood, liver/blood, and heart/blood ratios of acatalasemic mice after intraperitoneal injection of metallic mercury or after exposure to metallic mercury vapor were significantly higher than those of normal mice. These ratios of normal or acatalasemic mice after injection with metallic mercury or exposure to metallic mercury vapor were significantly higher than those of normal and acatalasemic mice injected with mercuric ion. The amount of metallic mercury exhaled from acatalasemic mice injected with metallic mercury was greater than that from normal mice, indicating that the level of metallic mercury in blood of the former was higher than that of the latter. Actually, metallic mercury in the blood of acatalasemic mice injected with metallic mercury is higher than that in the blood of normal mice, suggesting that metallic mercury is easily transfered from blood to brain, liver, kidney, and heart.     

Metabolism of lead-210 in juvenile and adult rhesus monkeys (Macaca mulatta)

Summary Experiments were conducted measuring the gastrointestinal absorption and elimination of a single dose of lead-210 acetate in infant and adult rhesus monkeys. Urinary and fecal excretion of absorbed lead was followed for 23 days. Infant monkeys eliminated less and absorbed more orally administered lead. Adult animals excreted more absorbed lead in feces, while urinary excretion between adults and infants was similar. Increased absorption of administered lead and reduced fecal excretion of absorbed lead resulted in significantly greater body burden of lead-210 in infant animals. Blood lead values were increased in the infant animals, and were inversely correlated with body burden and percent absorption of ingested lead.     

Metabolism of lead-210 in juvenile and adult rhesus monkeys (Macaca mulatta).

Experiments were conducted measuring the gastrointestinal absorption and elimination of a single dose of lead-210 acetate in infant and adult rhesus monkeys. Urinary and fecal excretion of absorbed lead was followed for 23 days. Infant monkeys eliminated less and absorbed more orally administered lead. Adult animals excreted more absorbed lead in feces, while urinary excretion between adults and infants was similar. Increased absorption of administered lead and reduced fecal excretion of absorbed lead resulted in significantly greater body burden of lead-210 in infant animals. Blood lead values were increased in the infant animals, and were inversely correlated with body burden and percent absorption of ingested lead.