Organ and subcellular distribution of cadmium in rats exposed to cadmium, mercury, and selenium

Four groups of rats were given: cadmium chloride (Cd), cadmium chloride and mercuric chloride (Cd + Hg), cadmium chloride and sodium selenite (Cd + Se), or cadmium chloride, mercuric chloride, and sodium selenite (Cd + Hg + Se). All animals received subcutaneous doses of 115mCdCl2 (0.3 mg Cd/kg) every other day for 2 weeks. Mercuric chloride was administered intravenously at doses of 0.5 mg Hg/kg every other day, and Na2 75SeO3 intragastrically at doses of 0.1 mg Se/kg every day for a fortnight. The whole-body and organ retention of cadmium changed slightly with the type of exposure. A significant interaction effect of the examined elements was noted in the nuclear and soluble fractions of the liver and kidneys. Mercury decreased the cadmium concentration in both the nuclear and soluble fractions of the kidneys and diminished the effect of selenium on the cadmium level in the soluble fraction of the kidneys. In the liver the presence of mercury contrary to selenium, lowered the cadmium level in the nuclear fraction. The pattern of cadmium binding to proteins of the soluble fraction of the kidneys and liver remained the same in all groups of animals.     

Organ and subcellular distribution of selenium in rats exposed to cadmium,mercury, and selenium

Three groups of rats were given sodium selenite (Se), sodium selenite and cadmium chloride (Se + Cd), or sodium selenite, cadmium chloride, and mercuric chloride (Se + Cd + Hg), respectively. All animals received subcutaneous doses of ¹¹⁵CdCl₂ (0.3 mg Cd/kg) every other day for a fortnight. Mercuric chloride was administered intravenously at doses of 0.5 mg Hg/kg every other day and Na₂⁷⁵SeO₃ intragastrically at doses of 0.1 mg Se/kg every other day for 2 weeks. The whole-body retention of selenium was slightly elevated by cadmium and increased threefold by cadmium with mercury (mainly blood, liver, and kidneys). Cadmium did not affect subcellular levels of selenium in the kidneys and slightly increased the selenium content in the soluble fraction of the liver. On the other hand, combined administration of mercury and cadmium induced a significant elevation of the selenium content in all subcellular fraction of the kidneys and in the nuclear and mitochondrial fractions of the liver. In all animal groups selenium was bound in the soluble fractions of both the liver and kidneys by high-molecular-weight proteins.     

Organ and subcellular distribution of mercury in rats as dependent on the time of exposure to sodium selenite.

Sodium selenite was administered to rats employing different sequence patterns: before, after, and simultaneously with mercuric chloride. All animal groups were given ²⁰³HgCl₂ intravenously at a dose of 0.5 mg Hg/kg, every other day for 2 weeks. Na₂SeO₃ was administered intragastrically, either as a single dose of 7.0 mg Se/kg or by repeated doses of 0.1 mg Se/kg each. Administration of sodium selenite after saturation of the organism with mercury did not change essentially the mercury level in the kidneys while bringing about a decrease of the level of this metal in the liver and a considerable accumulation of mercury in the blood. In the case of other forms of exposure, selenium decreased the level of mercury in the kidneys, the highest changes of the binding of this metal being observed for the soluble fraction. In the nuclear fraction of this organ the level of mercury did not change irrespective of the sequence of administration and of the selenium dose. In the liver, an increased retention of mercury was found, especially in the nuclear and mitochondrial fractions. The highest interaction effect was attained only in the case of simultaneous administration of equimolar amounts of both elements.     

Effects of selenium on mercury-induced renal lesions and on subcellular mercury distribution

The effects of selenite on the renal tubular lesion caused by mercuric chloride were studied by electron microscopy using male rats injected with HgCl₂ and/or Na₂SeO₃. The protective effect of selenite on mercury-induced renal injuries was confirmed both in proximal tubular cells and in glomerulus. Mercury specifically deposited in lysosomes in proximal tubular cells of rats which received either mercury alone or mercury plus selenite, although the density of fine gold grains, which revealed the mercury deposits, appeared to be higher in the rats treated with mercury alone than in those administered mercury and selenite. These observations by electron microscopic histochemistry were consistent with the analytical data for mercury in the kidneys. The results suggest that the reduction of renal mercury toxicity by selenite should be ascribed not to the change in subcellular mercury localization but to the decrease in the level of mercury in kidneys.     

Changes in activity of malate dehydrogenase and glucosephosphate isomerase in serum of rats exposed chronically to inorganic mercury and its aryl and alkyl compounds

Summary In course of prolonged exposure /14 weeks/ to various mercury compounds /MetHg — a fluid seed-dressing preparation 0,8, Phenyl and Ethyl chlorides and.HgCl₂ in doses corresponding to 5% of DL₅₀/3 times weekly/, enhanced levels of activity of malate dehydrogenase /MDH/ and glucosephosphate isomerase /PHI/ in blood serum were observed. After 7 weeks of exposure about fourfold increase of MDH and 2-3-fold enhancement of PHI activities were found relative to controls. After 14 weeks of exposure in livers of rats, given MetHg and EtHg, organic mercury was found at concentrations of 28,8 and 4 g/g tissue, respectively. Inorganic mercury in liver was found in animals given all compounds and concentrations were in the range of 1,2 – 4,7 g/g tissue.The study was partly subsidised by the Polish-American agreement 05-009-2 with the National Institute of Occupational Safety and Health, PHS, USA. Chief investigator — doc. dr hab. O.K. Piotrowski.     

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.     

Effect of administration sequence of mercuric chloride and sodium selenite on their fates and toxicities in mice

Interaction of mercury and selenium was examined in mice given mercuric chloride (25 μmol/kg) intravenously with sodium selenite (25 μmol/kg, iv) according to various administration schedules. Body weight of the mice given mercuric chloride or selenite alone did not increase, but the mice given both compounds simultaneously grew as well as control mice. On the other hand, only a 1-hr shift of administration of either compound canceled the mutual detoxifying effect. The most conspicuous changes in tissue distribution of mercury and selenium and in gel filtration patterns of both elements accumulating in tissues of the mice were observed when both compounds were administered simultaneously. These experimental results indicate that the interaction of mercuric mercury with selenite in mice occurred to the greatest extent upon simultaneous administration, supporting the hypothesis that the interaction primarily occurs in the blood stream.     

Occupational Health and Accidents in Feldspar Mining

The percentage of whole-body mercury found in the lungs of guinea pigs exposed to mercury vapor for ten minutes was in the same range as after one hour’s exposure (25% to 33%). The highest concentrations of mercury were found in peripheral lung structures. The same distribution was found at different concentrations of mercury in the air. Only one tenth of the values were found in corresponding structures of animals injected with mercuric nitrate. Most of the mercury deposited in alveolar tissues is therefore probably deposited there directly from the air. The results are considered to indicate the following: that mercury vapor penetrates to the alveoli; that most of it is quickly transferred to the blood; and that a small fraction is deposited in the pulmonary tissues, from where it is slowly eliminated to the rest of the body.     

The influence of selenium on the level of mercury and metallothionein in rat kidneys in prolonged exposure to different mercury compounds

Mercuric chloride, phenylmercuric chloride, ethylmercuric chloride /0,23 mg Hg/kg/ and methylmercurycyan guanidine /0,46 mg Hg/kg/ were orally administered to rats every second day for 14 weeks. The same doses of the above mentioned mercury compounds were administered alternately with sodium selenite /0,18 mg Se/kg/ to parallel groups of rats at the same time. The level of total and inorganic mercury and of metallothionein was determined. All mercury compounds increased the level of metallothionein in rat kidneys. In rats which received only selenium the level of metallothionein was twice lower in the kidneys in relation to the physiological level of this protein. Selenium eliminated the stimulation of biosynthesis of metallothionein by mercury.     

The influence of selenium on the level of mercury and metallothionein in rat kidneys in prolonged exposure to different mercury compounds

Summary Mercuric chloride, phenylmercuric chloride, ethylmercuric chloride /0,23 mg Hg/kg/ and methylmercurycyan guanidine /0,46 mg Hg/kg/ were orally administered to rats every second day for 14 weeks. The same doses of the above mentioned mercury compounds were administered alternately with sodium selenite /0,18 mg Se/kg/ to parallel groups of rats at the same time. The level of total and inorganic mercury and of metallothionein was determined. All mercury compounds increased the level of metallothionein in rat kidneys. In rats which received only selenium the level of metallothionein was twice lower in the kidneys in relation to the physiological level of this protein. Selenium eliminated the stimulation of biosynthesis of metallothionein by mercury.The study was partly subsidised by the Polish-American agreement 05-009-2 with the National Institute of Occupational Safety and Health, PHS, USA, Chief investigatorprof. dr hab. J.K. PIOTROWSKI.     

In vitro effects of selenite and mercuric chloride on liver thiobarbituric acid-reactive substances and non-protein thiols from rats: influences of dietary cholesterol and polyunsaturated and saturated fatty acids

OBJECTIVE: We measured the in vitro effects of mercuric chloride (Hg2+) and selenite (Se4+) on hepatic 2-thiobarbituric acid-reactive substances (TBARS) and non-protein sulfhydryl (NPSH) levels of rats fed diets enriched with polyunsaturated or saturated fatty acids with and without cholesterol. METHODS: Male Wistar rats (21 d old) were assigned to one of four groups and fed diets containing 20% soybean oil, 20% soybean oil plus 1% cholesterol, 20% coconut oil, or coconut oil plus 1% cholesterol. After the feeding period (6 wk), body weight gain was equal in all groups. TBARS levels and NPSH content were measured after in vitro exposure to mercuric chloride (100 microM) and sodium selenite (25 microM) for 1 h. RESULTS: The lipid peroxidation, measured as TBARS levels in the control group, were statistically higher in hepatic homogenates of rats fed diets containing soybean oil than in groups fed coconut oil (P = 0.009). However, cholesterol supplementation did not change TBARS levels. Selenite alone did not modify TBARS production, whereas mercury alone significantly increased TBARS levels. Moreover, Se4+ protected against mercury-induced lipid peroxidation only in rats fed diets containing coconut oil. In the control group, dietary fat acids did not change NPSH levels. Selenite produced higher oxidative effects toward NPSH content, whereas Hg2+ decreased NPSH levels only in liver from rats fed diets containing soybean oil. NPSH levels were higher after concomitant exposure to Se4+ and Hg2+ chloride that after exposure to Se4+ alone, suggesting an interaction between Hg2+ and Se4+. Catalase activity was higher in animals fed diets containing soybean oil. Dietary cholesterol decreased glutathione peroxidase activity. CONCLUSION: Together these results indicated that the protective effect of Se4+ against mercury-induced lipid peroxidation depends on dietary fat saturation.     

The influence of age on the gastrointestinal absorption of mercuric chloride and methyl mercury chloride in the rat

The intestinal absorption of mercuric chloride and methyl mercury chloride was determined in neonatal (6-day-old) and mature (7-week-old) rats. No differences between the two age groups were observed in the absorption of methyl mercury chloride (0.08 μg Hg/ml) determined up to 2 hr after administration in vivo into closed segments of the duodenum or ileum. In contrast, the 1-hr duodenal absorption of mercuric chloride (8 μg Hg/ml) was significantly greater in neonatal animals (18.1%) as compared to 23-day-old weanling (7.3%) or mature (3.6%) animals. Ileal absorption of mercuric chloride was also higher in neonates than in mature animals, but the magnitude of the difference was less than that observed in the duodenum. GI absorption of mercuric chloride (46 μg Hg/kg) was also assessed in neonatal, weanling, and mature rats at 4 and 43 hr after gastric intubation. The percentage of the dose in the carcass, determined after removal of the GI tract, was significantly higher at both times in neonatal and weanling rats as compared to mature animals. Analysis of mercury content in the gastrointestinal tract of these animals also indicated age-dependent differences in mercury transit through the GI lumen. The extent of gastric emptying of mercury by 4 hr after dosing was significantly less in neonatal and weanling rats compared to mature animals. In addition, the small intestinal transit of mercury was markedly slower in neonates with 74.8% of the dose in the GI tract after 43 hr as compared to 5.2% and 3.0% in weanling and mature animals, respectively. These findings indicate that in the neonate, exposure to inorganic mercury by the oral route can be expected to result in higher systemic, as well as small intestinal, levels of mercury because of enhanced GI absorption and decreased luminal transit, respectively.     

Histochemical demonstration of mercury in the olfactory system of salmon (Salmo salar L.) following treatments with dietary methylmercuric chloride and dissolved mercuric chloride

The deposition of organic and inorganic mercury compounds was studied histochemically in the salmon (Salmo salar L.) olfactory system. One group of salmon was given fodder pellets containing methylmercuric chloride (CH3HgCl, 99 micrograms Hg/g) for 4 weeks. Other groups of fish were exposed to dissolved mercuric chloride (HgCl2, 270 micrograms Hg/liter) for 2, 6, and 12 hr, respectively. In both series of experiments, the radioisotope 203Hg was included in order to determine the accumulation of mercury in the olfactory system. Gamma-spectrometry showed that both mercury compounds accumulated in the olfactory rosettes and their nerves. Tissue sections from the rosettes and olfactory nerves were subjected to autometallographic silver enhancement, thereby rendering mercury deposits visible for light and electron microscopy. Microscopic analysis demonstrated an intense and comprehensive Hg deposition in the axons and Schwann cells of both methylmercury- and inorganic mercury-exposed fish. On the other hand, the two mercury compounds showed different staining patterns in the sensory epithelium. The silver grains evoked by methylmercury were localized predominantly in lysosome-like inclusions within the receptor cells, while those produced by HgCl2 exposure were situated mainly along the borders of neighboring cells. The present findings that organic and inorganic mercury compounds were deposited in the olfactory system along its whole length, from the receptor cell apices to the brain, support the electrophysiological results presented elsewhere (Baatrup et al., 1990, Ecotoxicol. Environ. Safety 20, 269-276).     

硒对汞致小鼠淋巴细胞DNA损伤的影响

目的　探讨硒对汞致小鼠淋巴细胞DNA损伤的拮抗作用。方法　小鼠同时或先后经腹腔注射 0 .9、0 .3 和0 .1 mg/kg亚硒酸钠与1 .0mg/kg氯化汞水溶液,1次/ d,连续处理2 d;采用单细胞凝胶电泳实验研究上述处理对小鼠淋巴细胞DNA损伤的影响。结果　不同剂量的硒和汞同时染毒时,高硒组其DNA平均迁移长度极显著低于单独汞组(P<0 .01);染汞之前给硒,与单独汞组比较,加硒组其DNA平均迁移长度极显著降低(P<0. 01),且中、低剂量组降低更为明显;染汞之后给硒,3个加硒组其 DNA平均迁移长度极显著低于单独汞组(P<0 .01),硒剂量越高,降低越明显。结论　硒对汞致淋巴细胞DNA损伤有拮抗作用,但这一作用和其染毒剂量及染毒顺序有关。     

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.     

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.     

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.     

Relationship of membrane-bound sulfhydryl groups to vitamin D-stimulated uptake of [75Se]Selenite by the brush border membrane vesicles from chick duodenum

The uptake of selenite by purified brush border membrane vesicles isolated from duodena of rachitic or vitamin D-treated chicks was studied by using radioactive selenite and a rapid filtration technique. Cholecalciferol treatment (500 IU at 72 h) significantly enhanced selenite uptake, a response that decreased when the vesicles were stored at room temperature for 2.5 h prior to the uptake measurement. Preincubation of the vesicles in 1.0 mmol/L H2O2 reduced [75Se]selenite uptake, indicating the involvement of oxidizable groups in the uptake reaction. Iodoacetic acid (IAA), a sulfhydryl-blocking reagent, at 1-2 mmol/L concentration eliminated the difference in selenite uptake due to cholecalciferol and had no effect on vesicles from rachitic animals. A higher concentration of IAA (10 mmol/L) enhanced selenite uptake manyfold and increased the absolute difference due to cholecalciferol treatment. Single intravenous doses of 100 IU cholecalciferol, 100 IU ergocalciferol, or 0.1 micrograms 1,25-dihydroxycholecalciferol also stimulated selenite uptake, suggesting a general response to vitamin D compounds. Normal animals given a single dose of 1,25-dihydroxycholecalciferol 12 h prior to killing also responded. Treatments that enhanced the uptake of [75Se]selenite also increased the amount of membrane-bound sulfhydryl groups, suggesting the involvement of membrane-bound sulfhydryl groups in the vitamin D response. A significant increase in selenite uptake by intravenous 1,25-dihydroxycholecalciferol occurred within 10 min. This rapid effect provides a new tool to probe early biochemical effects of vitamin D on intestinal epithelium.     

Urinary mercury excretion and proteinuria in pathology laboratory staff.

The use of mercuric chloride as an histological fixative was associated with high environmental atmospheric concentrations of mercury vapour (up to 0-5 nmol/l) as well as mercury compounds (total Hg to 1-0 nmol/l). Technicians exposed to this environment showed increased urinary mercury (median value 265 nmol/24h) and protein outputs (median value 117 mg protein/24h). Routine control measures, ventilation and careful handling of mercuric chloride solutions, reduced the level of atmospheric mercury vapour levels to within acceptable limits (threshold limit values 0-01 mg/m3 (0-05 nmol/l) alkul compounds and 0-05 mg/m3 (0-25 nmol/l) for all forms except alkyl). This reduction was associated with the disappearance of trace proteinuria from the technicians' urine. Contamination of histology laboratories by mercuric chloride should be minimised.     

Ozone Toxicology

Rats, rabbits, and monkeys were exposed to mercury vapor (1 mg/cu m) for four hours, and uptake and distribution of mercury in the brain was compared with that of animals injected intravenously with the same dose of mercury as mercuric salts. Vapor-exposed animals showed a brain content about ten times higher than the injected animals. The results indicate that the higher uptake in brain following vapor exposure is a general phenomenon in mammals.