Effect of mercuric chloride and methylmercury chloride exposure on tissue concentrations of six essential minerals

There are few data on the effects of mercury exposure on tissue concentrations of essential minerals. Male Sprague-Dawley rats were exposed to mercuric chloride and methylmercury chloride administered via the drinking water. Subsequently, the kidneys, spleen, liver, and brain were analyzed for mercury, calcium, copper, magnesium, manganese, iron, and zinc by atomic absorption spectrophotometry. Significant differences from controls were found for brain copper, kidney copper, and kidney zinc in the mercuric chloride-exposed animals; and for brain iron, kidney copper, kidney iron, kidney magnesium, spleen magnesium, and liver manganese in the methylmercury chloride-exposed rats. There was a fivefold higher mean kidney copper concentration in the mercuric chloride-exposed group; this may be related to the induction of renal metallothionein synthesis by mercury. Increased kidney copper may be a manifestation of heavy metal-induced renal toxicity. Both inorganic and methylmercury exposure produce significant changes in tissue concentrations of some essential minerals.     

Rapid changes in concentrations of essential elements in organs of rats exposed to methylmercury chloride and mercuric chloride as shown by simultaneous multielemental analysis

An in vivo study of rats given a dominant lethal dose of methylmercury chloride (MMC) or mercuric chloride (HgCl2) was conducted to elucidate the rapid biotransformation of essential elements. The elements were measured by inductively coupled plasma atomic emission spectrometry. For the rat brain Zn concentrations were higher in the MMC group than in the HgCl2 and control groups. The highest Cu concentration was found in HgCl2 dosed rat liver. For the rat kidney the highest Zn concentration was seen in the MMC group. From principal component analysis on the time dependent behaviour of each element in rat organs, characteristics specific to Cu in the liver and kidney and Mn in the brain were found after exposure to HgCl2 and Ca and Zn in the brain after exposure to MMC.     

Rapid changes in concentrations of essential elements in organs of rats exposed to methylmercury chloride and mercuric chloride as shown by simultaneous multielemental analysis.

An in vivo study of rats given a dominant lethal dose of methylmercury chloride (MMC) or mercuric chloride (HgCl2) was conducted to elucidate the rapid biotransformation of essential elements. The elements were measured by inductively coupled plasma atomic emission spectrometry. For the rat brain Zn concentrations were higher in the MMC group than in the HgCl2 and control groups. The highest Cu concentration was found in HgCl2 dosed rat liver. For the rat kidney the highest Zn concentration was seen in the MMC group. From principal component analysis on the time dependent behaviour of each element in rat organs, characteristics specific to Cu in the liver and kidney and Mn in the brain were found after exposure to HgCl2 and Ca and Zn in the brain after exposure to MMC.     

Alteration of inorganic mercury accumulation due to selenite in organs of mice fed methylmercury

Mice were fed methylmercury (10 nmol/g feed) and selenite (0, 8, 20 or 50 nmol/ml drinking water) for one or two weeks. Doses of selenite and duration of feeding were determining factors of total mercury and inorganic mercury concentrations in organs. Increasing the dose of selenite produced the following results: concentration of total mercury increased in the brain and liver and decreased in the blood, kidneys and spleen; concentration of inorganic mercury increased in the liver and spleen, decreased in the kidneys, and remained unchanged in the brain; the rate of inorganic mercury to total mercury increased in the liver and spleen, decreased in the brain, and remained unchanged in the kidneys. In every case, inorganic mercury in the blood was below the detection limit.     

Subchronic effects of methylmercury on plasma and organ biochemistries in great egret nestlings

In recent years, high concentrations of mercury have been found in wading birds in Florida, USA. Great egret (Ardea alba) chicks (2 weeks old) were dosed orally daily with the equivalent of 0, 0.5, or 5 microg/g Hg as methylmercury chloride in the diet for up to 12 weeks. Weakness of the legs or paralysis occurred in all high-dosed birds. Geometric mean blood Hg concentrations were 0.17, 10.3, and 78.5 microg/g (wet wt), respectively. Mercury concentrations for organs (microg/g wet wt), including brain (0.22, 3.4, and 35, respectively), liver (0.34, 15.1, 138, respectively), and kidney (0.28, 8.1, and 120, respectively), increased in a dose-dependent manner. Total glutathione (GSH) peroxidase activity was significantly lower in the plasma, brain, liver, and kidney of the high-dosed group. Plasma aspartate aminotransferase activity increased with mercury treatment, whereas lactate dehydrogenase activity decreased. Four other plasma chemistries were decreased significantly in the high-dosed group and included uric acid, total protein, albumin, and inorganic phosphorus. Lipid peroxidation increased in liver (low and high dose) and brain (high dose). Tissue changes in concentrations of reduced thiols included decreased total thiols and protein-bound thiols in liver, decreased protein-bound thiols in kidney, and increased GSH in kidney and brain. Activities of GSH S-transferase and oxidized glutathione reductase increased in liver. In kidney, GSH S-transferase and glucose-6-phosphate dehydrogenase activities increased with mercury dose. These findings, including apparent compensatory changes, are compared to other Hg studies where oxidative stress was reported in egrets, herons, and diving ducks in the field and mallards in the laboratory.     

Excretion and Absorption of Methyl Mercury After Polythiol Eesin Treatment

A synthetic polythiol resin when added to food at a concentration of 1% doubled the rate of excretion of mercury from mice given a single dose of methyl mercuric chloride. After 42 days of resin treatment the levels of mercury in blood, brain, kidney, and liver had been reduced by factors of 7.2, 6.0, 7.2, and 10.0, respectively, as compared with those in untreated animals. The resin also reduced by 50% the rate of absorption of methyl mercury compounds from food.     

Distribution of inorganic and methylmercury among tissues in mink (Mustela vison) and otter (Lutra canadensis)

Total mercury and methylmercury concentrations were measured in brain, kidney, liver, and fur from several mink and otter collected in south-central Ontario. There was a large range in concentrations of both total and methylmercury. The percentage of the total mercury present as methylmercury varied among the various tissues; however, the percentage mercury found as the methyl form was relatively constant within a given tissue for all tissues in mink but highly variable in otter. For both species the highest percentage of methylmercury was found in the brain, whereas the lowest percentage was found in the kidneys for the otter and in the fur for the mink. Comparison of mercury concentrations in otter reveals that animals with higher body fat have higher mercury concentrations. Measurements of mercury in fur can be used as a general indicator of internal tissue concentrations.     

Form of Dietary Methylmercury does not Affect Total Mercury Accumulation in the Tissues of Zebra Finch

Exposure to mercury in humans, other mammals, and birds is primarily dietary, with mercury in the methylated form and bound to cysteine in the tissues of prey items. Yet dosing studies are generally carried out using methylmercury chloride. Here we tested whether the accumulation of total mercury in zebra finch blood, egg, muscle, liver, kidney or brain differed depending on whether dietary mercury was complexed with chloride or cysteine. We found no effect of form of mercury on tissue accumulation. Some previous studies have found lower accumulation of mercury in tissues of animals fed complexed mercury. Much remains to be understood about what happens to ingested mercury once it enters the intestines, but our results suggest that dietary studies using methylmercury chloride in birds will produce similar tissue accumulation levels to those using methylmercury cysteine.     

Mercury uptake in vivo by normal and acatalasemic mice exposed to metallic mercury vapor (203Hg degrees) and injected with metallic mercury or mercuric chloride (203HgCl2)

Levels of mercury in the brain and liver of acatalasemic mice immediately following exposure to metallic mercury vapor or injection of metallic mercury were higher than those found in normal mice. Acatalasemic mice had decreased levels of mercury in the blood and kidneys when the levels were compared with those of normal mice, which indicated that catalase plays a role in oxidizing and taking up mercury. Thus, the brain/blood or liver/blood ratio of mercury concentration in acatalasemic mice was significantly higher than that of normal mice. These results suggest that metallic mercury in the blood easily passed through the blood-brain or blood-liver barrier. The levels of mercury distribution to the kidneys of normal and acatalasemic mice, 1 hr after injection of mercuric chloride solution, were higher than that of normal and acatalasemic mice, respectively, 1 hr after injection of metallic mercury.     

Effect of Selenium Pretreatment in Chronic Mercury Intoxication in Rats

Effect of selenium pretreatment (0.2 mg/kg/day, as sodium selenite), 4 h prior to mercury treatment (0.4 mg/kg/day, as mercuric chloride), administered intraperitoneally, was examined after daily exposure for 20 days’ in rats. Liver, kidney and brain tissues were assayed for malondialdehyde (MDA) level, glutathione (GSH) content and mercury concentration. Mercury induced MDA levels, which was also observed in selenium pretreated animals. Significant reduction in GSH levels was observed in mercury alone and selenium pretreated animals. Mercury accumulation was in the order of kidney, liver and brain. Selenium pretreatment resulted in further enhancement in mercury accumulation in liver and kidney.     

锌对氯化汞免疫毒性的影响及其机理

为了探讨锌对氯化汞免疫毒性的影响,采用免疫毒理学和生化毒理学方法观察氯化汞染毒的ＩＣＲ小鼠血中碳廊清率、绵阳红细胞（ＳＲＢＣ）致敏小鼠迟发型过敏反应（ＤＴＨ）、二硝基氯苯（ＤＮＣＢ）所致的迟发型皮肤过敏反应（ＤＣＨ）、血清溶血素（ＨＣ５０）和免疫脏器系数,结果显示：上述指标均明显低于对照组;预先给予醋酸锌后再给同剂量氯化汞的小鼠上述各指标均有不同程度提高;免疫器官脂质过氧化作用,汞组脂质过氧化物（     

Dose-dependence of methylmercury metabolism. A study of distribution: biotransformation and excretion in the squirrel monkey.

The distribution and excretion of different body burdens of methylmercury (MeHg) have been investigated in the squirrel monkey. In monkeys given weekly 0.8 mg/kg doses, orally, of 203-MeHg, a linear correlation was observed between the concentrations of radioactive Hg in the blood and brain to as much as a blood concentration of 1 mug/gm. Above this level, the ratio of concentration in the brain and blood was increased. The total Hg concentration in bile collected from the bile duct was 10% to 30% of that in blood, while the concentration in bile from the gallbladder approached that in the blood. The total Hg concentration in feces was always more than ten times that in urine. Biotransformation of MeHg to inorganic mercury has been demonstrated; in the liver about 20% of the total mercury was inorganic, in the kidney 50%, and in the bile 30% to 85%. In the brain less than 5% of the total mercury was inorganic. After a single 0.8 mg/kg dose, orally, of 203-MeHg, the halftime for total Hg in blood was 49 plus or minus 2.8 days, and in the whole body 134 plus or minus 2.7 days. During the first four days after dosing, the decrease in blood concentration was more rapid than that occurring later, due to a redistribution within tissue compartments. A differential distribution of MeHg within the brain has been demonstrated in animals that showed clinical signs of intoxication.     

The effect of cadmium pretreatment on the disposition and excretion of methylmercury and trace elements (zinc, copper) in rats

Cadmium chloride (Cd) was injected s.c. into male rats at a dose rate of 3 mg Cd/kg 3 times a week for 4 weeks. The animals were maintained for administration of methylmercury (203 Hg) chloride at a dose of 3 mg CH3Hg/kg given p.o. 3 times a week for 2 weeks, followed by 3 weeks of recovery period. Animals were sacrificed 24 h after the final dose of MeHg, or 5 weeks after cessation of Cd administration. Cd-pretreatment significantly decreased total Hg concentration in the kidney and RBC and almost completely inhibited demethylation of MeHg in the kidney (from 32% to 3% of inorganic Hg). Cd-pretreatment did not affect urinary excretion of total Hg, but significantly increased daily excretion of total Hg in feces. MeHg given alone significantly increased renal but not hepatic copper levels and decreased copper in the plasma and brain. In Cd-pretreated rats, both renal and hepatic copper concentration were in the normal ranges. Zinc levels in Cd-pretreated rats significantly increased in the kidney, liver and brain but decreased in plasma (compared to control and MeHg-alone treated animals). From these results it can be concluded that Cd-pretreatment may decrease MeHg toxicity by increasing the fecal mercury excretion and by inhibiting the formation of inorganic mercury in the kidney, which is a more potent renal toxin than MeHg.     

Dose-Dependence of Methylmercury Metabolism

The distribution and excretion of different body burdens of methylmercury (MeHg) have been investigated in the squirrel monkey. In monkeys given weekly 0.8 mg/kg doses, orally, of ²⁰³MeHg, a linear correlation was observed between the concentrations of radioactive Hg in the blood and brain to as much as a blood concentration of 1μg/gm. Above this level, the ratio of concentration in the brain and blood was increased.

The total Hg concentration in bile collected from the bile duct was 10% to 30% of that in blood, while the concentration in bile from the gallbladder approached that in blood. The total Hg concentration in feces was always more than ten times that in urine.

Biotransformation of MeHg to inorganic mercury has been demonstrated; in the liver about 20% of the total mercury was inorganic, in the kidney 50%, and in the bile 30% to 85%. In the brain<5% of the total mercury was inorganic. After a single 0.8 mg/kg dose, orally, of ²⁰³MeHg, the halftime for total Hg in blood was 49±2.8 days, and in the whole body 134±2.7 days. During the first four days after dosing, the decrease in blood concentration was more rapid than that occurring later, due to a redistribution within tissue compartments. A differential distribution of MeHg within the brain has been demonstrated in animals that showed clinical signs of intoxication.     

Sexual differences in the distribution and retention of organic and inorganic mercury in methyl mercury-treated rats

At 56 days of age, male and female Long-Evans rats received 1 mumole of 203Hg-labeled methyl mercuric chloride per kilogram sc and total, organic, and inorganic mercury contents and concentrations in tissues were determined for up to 98 days postdosing. Whole body clearance of mercury was faster in females than in males, and females attained higher peak percentages of the methyl mercury dose in kidney and brain than did males. Females had significantly higher mean percentages of the mercury dose present in the kidney and brain as organic or total mercury and in brain as inorganic mercury than did males. Males had significantly higher mean percentages of the dose present as organic or total mercury in pelt and whole body than did females. When expressed on a concentration basis, the only significant sexual difference was in the higher average concentration of organic mercury in the kidneys of females. When expressed on a tissue content basis, significant male-female differences in the kinetics (sex X time interactions) of organic mercury retention were found in kidney, brain, skeletal muscle, pelt, and whole body. Significant sex X time interactions in the concentrations of organic mercury were found in kidney, skeletal muscle, and whole body. Kinetics of retention and concentration of inorganic Hg in the pelt differed significantly for males and females. Discordance in degree of statistical significance of differences in mercury contents and concentrations reflected in part differences in relative body composition of males and females. Integrated exposures of tissues of males and females to organic or inorganic mercury were determined by fitting multiexponential retention functions to retention data. Differences in integrated exposure were estimated by the female-to-male ratio of areas under retention curves. Reconstruction of whole body organic and inorganic mercury burdens from constituent tissues indicated that integrated exposures of males and females to inorganic mercury were equal but females had a lower integrated exposure to organic mercury. Integrated exposure of liver to either form of mercury was about equal in males and females. However, the integrated exposure of the brain of females to inorganic mercury was 2.19 times that of males suggesting a sexual difference in accumulation or retention of inorganic mercury in the nervous system. These sexual differences in distribution and retention of organic and inorganic mercury after methyl mercury exposure may underlie reported sexual differences in sensitivity to the toxic effects of methyl mercury.     

Generation and dose as modifying factors of inorganic mercury accumulation in brain, liver, and kidneys of rats fed methylmercury

Through three generations, male rats were fed a commercial chow supplemented with four levels of methyl mercury; the average mercury concentrations were 0.038, 0.18, 7.23, and 33.92 nmol Hg/g food for control, low, middle, and high dose groups, respectively. No clinical abnormalities except enlarged kidneys were found in these animals. The effects of dose and generation on tissue distribution and accumulation of inorganic mercury and total mercury were studied in the brain, kidneys, and liver. The dose level of methyl mercury greatly determined the organ accumulation of total mercury and inorganic mercury, as well as the ratio of inorganic mercury concentration to total mercury concentration (I/T) in organs. The I/T ratio was inversely related to the dose level of methyl mercury. With generational procession, the most notable change was found in the liver, i.e., the increasing I/T ratio and the decreasing total mercury accumulation at any dose level. In contrast, the I/T ratio in the kidney showed no constant tendency with generation. The present results suggest that the generational enhancement of inorganic mercury formation from methyl mercury occurs mainly in the liver.     

外源性超氧化物歧化酶对氯化汞免疫毒性的影响

采用免疫毒理学方法观察外源性ＳＯＤ对汞的免疫毒性的影响。结果氯化汞染毒的ＩＣＲ小鼠血中碳廓清率、ＳＲＢＣ致敏小鼠迟发型过敏反应（ＤＴＨ），ＤＮＣＢ所致的迟发型皮肤过敏反应（ＤＣＨ），血清溶血素（Ｈｃ５０）和免疫脏器系数均明显低于对照组，预先给予ＳＯＤ后再给同剂量氯化汞的小鼠除Ｈｃ５０外上述各指标均有不同程度提高。免疫器官脂质过氧化作用，汞组脂质过氧化物（ＬＰＯ）含量明显高于对照组，ＳＯＤ活性比对照组明显降低（Ｐ＜０．０１），而ＳＯＤ－汞组与汞组比较，ＬＰＯ含量明显降低，ＳＯＤ活性明显升高（Ｐ＜０．０５）。提示外源性ＳＯＤ能拮抗氯化汞所致的免疫毒性和脂质过氧化作用。     

Distribution of Trace Metals and Methylmercury in Soft Tissues of the Freshwater Eel Anguilla marmorata in Vietnam

This study investigated trace metals in water, sediment, and various organs of the mature eel Anguilla marmorata in the Ba River, Vietnam. The metal concentrations in water and sediment did not exceed the Vietnam water criteria and sediment background concentration, except for Mn and Pb in sediment. The results of metal analysis in eel specimens indicated that the liver and kidney were the dominant organs for almost all trace metals, whereas muscle tended to accumulate high levels of Hg and approximately 87.4–100% of Hg was methylmercury. A strong positive correlation between mercury levels in muscle and age were found, but there was no correlation between mercury and body size. Interestingly, a high concentration of Zn was found in the gonad and liver; this indicated that high levels of Zn in the liver might play a physiologically important role in the eel’s biological mechanisms during gonadal maturation. Though almost none of the metal concentrations in the muscle exceeded the reference doses of the U.S. EPA, approximately 80% of eels from the river contained mercury exceeding the recommended levels (0.30 μg/g) of the U.S. EPA and might present a risk for human consumption.     

氯化甲基汞染毒对亲仔两代ICR小鼠脑、肝、肾中汞分布的影响

[目的]通过ICR孕鼠饮水接触低剂量氯化甲基汞,研究汞在亲仔两代小鼠脑、肝、肾及血清中的分布及其相关性。[方法]ICR孕鼠随机分为对照组、低剂量组(0.01mg/L)和高剂量组(0.10mg/L),于怀孕第6天起分别自由饮用蒸馏水及氯化甲基汞含量分别为0.01、0.10mg/L的蒸馏水直至哺乳期结束,用原子荧光法测定汞在各脏器内的含量,并做血清汞和脏器汞含量的相关性分析。[结果]在低剂量甲基汞作用下,亲仔两代未出现明显的毒性反应。随着染毒剂量的增加,亲仔两代小鼠血清中的总汞含量增加,对照组、低剂量组和高剂量组母鼠血清中总汞含量分别为1.228、2.358和6.195μg/L,仔鼠为0.801、3.217和3.763μg/L,高剂量组和对照组间差别有显著性(P<0.05);随着染毒剂量的增加,各脏器中的总汞含量也增加,对照组、低剂量组和高剂量组母鼠肾脏总汞含量分别为13.890、25.780、253.980ng/g组织湿重,肝脏为3.710、11.520、100.820ng/g组织湿重,脑组织为2.820、3.070、23.810ng/g组织湿重;对照组、低剂量组和高剂量组仔鼠肾脏总汞含量分别为6.940、13.090、102.170ng/g组织湿重,肝脏为2.660、5.450、38.850ng/g组织湿重,脑组织为1.600、2.660、8.120ng/g组织湿重;母鼠和仔鼠脏器中总汞蓄积的模式一样:肾脏>肝脏>脑组织。在低剂量下,母鼠血清总汞含量与肝脏、肾脏、脑组织中的总汞含量的相关系数分别为0.830、0.967、0.802;在高剂量下,与肝脏、肾脏、脑组织的相关系数分别为0.997、0.833、0.850,均有较高的相关性(P<0.05)。而仔鼠在高剂量下血清总汞与肝脏、肾脏、脑组织的相关系数分别为0.737、0.672、0.702,其血清总汞和脏器总汞也有相关性(P<0.05);在低剂量时血清总汞与肝脏、肾脏、脑组织总汞的相关系数分别为0.040、0.300、0.080,没有相关性(P>0.05)。[结论]母鼠接触低剂量甲基汞即可在亲仔两代各脏器中蓄积,亲代血清总汞含量和脏器总汞含量具有明显的相关性;仔代在高剂量时血清总汞含量和脏器总汞含量有明显的相关性,而在低剂量下无相关性。     

Mercury concentration in organs of contemporary Japanese

Concentrations of inorganic mercury (IHg), methylmercury (MeHg), and total mercury (THg) were determined for autopsy samples from 46 Japanese subjects. Two laboratories (Labs A and B) participated in Hg analyses: Lab A for THg and IHg and Lab B for THg and MeHg. Total mercury concentration values were in good agreement between the two laboratories: the averages were several hundreds of ng/g in kidney cortex, kidney medulla, and liver, and were several tens of ng/g in cerebrum, cerebellum, heart, and spleen. Inorganic mercury accumulated more in kidney and liver: its percentage THg was 81-84% in the kidney, 67% in the liver, 25% in the heart, 22% in the spleen, 20% in the cerebrum, and 14% in the cerebellum. Methylmercury levels in tissues were uniform through all organs except the liver. Approximately 80% was in the form of MeHg in the cerebrum, cerebellum, heart, and spleen, whereas the values were 33%, 15%, and 11% in the liver, kidney medulla, and kidney cortex, respectively. Age was a significant factor in increased IHg concentrations in the cerebrum and heart, decreased values of %MeHg in the cerebrum, cerebellum, and heart, and increased values of %IHg in the cerebrum and heart.