Subcellular Distribution Of Mercury Research Articles

Detoxification mechanism of heavy metals in marine mammals and seabirds: interaction of selenium with mercury, silver, copper, zinc, and cadmium in liver.

Subcellular distribution of mercury, selenium, silver, copper, zinc, and cadmium was determined in the liver of northern fur seals (Callorhinus ursinus), black-footed albatrosses (Diomedea nigripes), and Dall's porpoises (Phocoenoides dalli). Mercury, selenium, and silver were preferentially accumulated in nuclear, lysosomal, and mitochondrial fraction with an increase in their hepatic concentrations, whereas copper, zinc, and cadmium were accumulated mainly in cytosol with an increase in the hepatic concentrations for all three species. To gain insight into the existing state of the metals, they were extracted with four extractants--sodium dodecylsulfate (SDS); 2-mercaptoethanol; 2-mercaptoethanol + guanidinium thiocyanate; and copper sulfate (CuSO4)--at several concentrations from nuclear, lysosomal, and mitochondrial fraction in liver from a specimen of northern fur seal. Extraction efficiencies of the metals for 2-mercaptoethanol + guanidinium thiocyanate and CuSO4 were much higher than those for SDS and 2-mercaptoethanol. Also, for all individuals of the three species, metals were extracted by the three extractants--2% SDS; 0.25 mol/L 2-mercaptoethanol + 5 mol/L guanidinium thiocyanate; and 0.1 mol/L CuSO4--from nuclear, lysosomal, and mitochondrial fraction of liver. In the northern fur seals with higher concentration of mercury, the molar ratio of selenium to mercury approached unity in the nonextractable fraction of 0.25 mol/L 2-mercaptoethanol + 5 mol/L guanidinium thiocyanate, suggesting the possible formation of mercuric selenide (HgSe) with increasing hepatic concentration. Because the nonextractable content of mercury and its distribution were larger for black-footed albatross than those for the other two species, it was suggested that the black-footed albatross has a stronger ability to form a stable compound(s) of mercury in the liver. It is notable that the existing state of silver was similar to that of mercury as judged by their subcellular distribution and the extraction tests, suggesting that silver also interacted with selenium in the liver of marine animals used in this study.

Mercury binding proteins in liver and muscle of flat fish from the northern Tyrrhenian sea

1. The subcellular distribution of mercury and possible presence of Hg binding proteins of low molecular weight were investigated by ultracentrifugation and gel filtration in liver and muscle of the flat fish Citharus linguatula and Lepidorhombus boscii from the northern Tyrrhenian sea, heavily contaminated by the metal. 2. For both tissues, Hg contents were higher in the pellet than in the supernatant. 3. In the eluate of supernatant from Sephadex G-75 of both tissues, Hg was mainly bound to high molecular weight ligands. 4. Differently from the muscle eluate, that from liver also contained a consistent amount of Hg bound to low molecular weight ligands.

Protective effect of sodium molybdate on the acute toxicity of mercuric chloride. V. Enhancement of renal regeneration after exposure to HgCl 2

Pretreatment with Na 2MoO 4 protected rats from HgCl 2-induced decreases in the renal concentration of amino acids, RNA, DNA, ATP and dry matter. It also reduced the mercury-induced increases in renal water, Ca and serum creatinine. Ma 2MoO 4 considerably elevated the RNA/DNA ratio in the renal cortex after treatment with HgCl 2. In addition, subcellular distribution of mercury was markedly altered by pretreatment with Na 2MoO 4, specifically Na 2MoO 4 pretreatment decreased the mercury content in the particulate fractions such as the nuclei and mitochondria while increasing the mercury content of the cytosol. Sephadex G-75 gel filtration showed that the increase in mercury content in the cytosol of Na 2MoO 4-pretreated rats is due to an increase in the metal content of a metallothionein-like fraction. These results suggest that Na 2MoO 4-pretreatment protects against HgCl 2 renal toxicity by stimulating mercury-mediated metallothionein induction in the renal cortex and renal regenerative processes.

The effect of potassium dichromate and mercuric chloride on urinary excretion and organ and subcellular distribution of [ 203Hg]mercuric chloride in rats

The mechanism by which subthreshold/non-effective doses or concentrations of potassium dichromate (K 2Cr 2O 7) potentiate the effect of moderately effective dose/concentrations of mercuric chloride (HgCl 2) on renal organic ion transport is not understood. To investigate this effect, the rate of excretion of mercury from the intact animal and the renal and hepatic accumulation and subcellular distribution of mercury within kidney cortex following pretreatment or in vitro exposure to K 2Cr 2O 7 were undertaken. Coincidental administration of K 2Cr 2O 7 had no significant effect in altering the rate of excretion of labeled mercury. Organ distribution showed time dependence; however, the presence of K 2Cr 2O 7 did not increase renal mercury concentrations. In fact, significantly less mercury was found at 4 h in the kidneys of rats receiving both metal salts. Subcellular distribution of labeled mercury ( 203Hg) was also not significantly altered by the presence of K 2Cr 2O 7, although the distribution patterns for in vitro exposure and pretreated tissues were different. These studies show that K 2Cr 2O 7 does not produce alterations in urinary elimination, organ distribution or subcellular distribution of mercury.

Cellular uptake and subcellular distribution of mercury in chick embryonic retinal cell aggregates

Cellular uptake and subcellular distribution of mercury ( 203HgCl 2) were determined in the chick embryonic retinal cell aggregation system. The accumulation of mercury was dependent upon its concentration in the medium. The uptake was rapid; a maximum deposition of mercury at 5 μ M occurred within the first 30 min followed by a decline. Accumulation of mercury at 1 μ M was constant between 15 min and 24 hr. The subcellular distribution of mercury was observed in the following order: nuclei and cell debris > mitochondria-lysosomes > 105,000g supernatant > microsomes. The activity of acid phosphatase markedly decreased in the aggregates treated with mercury at 50 to 100 μ M for 24 hr. Low concentrations of mercury at 0.5 to 5 μ M showed an inhibition of this enzyme activity in a cell-free system. The results indicate a relationship between the amount of mercury in the cells and the toxicity it produced on the retinal cell aggregation system.

The influence of administered mass on the subcellular distribution and binding of mercury in rat liver and kidney.

The influence of the administered mass on the tissue and sub-cellular distribution of mercury (Hg) was investigated in rats, using 203Hg. The fraction of the dose deposited in liver increased threefold over the dose range 0.17-1.65 mg Hg X kg-1, while the retention in the kidney decreased by a factor of 2. The uptake in other organs, lung, spleen, brain, thymus, salivary glands showed no dose-dependent variation. Subcellular fractionation studies showed a dose-dependent increase in the Hg content of the liver cytosol, with corresponding decreases in the deposition in the lysosomal and nuclei-cell debris fractions. In contrast, no clear changes in the distribution of Hg amongst the subcellular organelles of the kidney were observed. The amount of Hg bound to metallothionein in the liver cytosol rose steeply with increasing dose. However, in the kidney cytosol the mass of Hg bound to metallothionein increased with dose up to 0.55 mg Hg X kg-1, thereafter remaining approximately constant. These observations suggest that the Hg-binding metallothionein in the kidney was saturated by administered doses greater than 0.55 mg Hg X kg-1, whereas in liver saturation levels of the metal were not reached even at the highest dose tested, 1.65 mg Hg X kg-1.

Renal cortical mercury distribution following dithiothreitol administration.

Previous studies from this laboratory have indicated that dithiothreitol (DTT) administration (31 mg DTT/kg, i.p.) 1 h after mercuric chloride injection (3 mg/kg, i.v.) results in partial reversal of Hg-induced renal toxicity without altering total renal mercury deposition. Studies were performed, therefore, to determine if DTT administration altered the renal delivery, excretion, and/or, in particular, subcellular distribution of mercury in a way that may explain the observed phenomenon. Analysis of mercury partitioning between red cells and plasma revealed no difference in relative distribution when Hg- or Hg + DTT-treated groups were compared. However, absolute mercury concentration in both whole blood and plasma of Hg + DTT-treated rats was significantly higher than in the Hg-treated group. Total urinary excretion of mercury was significantly less in Hg + DTT-treated rats than in rats treated with mercury alone. The subcellular distribution of mercury in the particulate and supernatant fractions of renal cortical homogenates from Hg-treated and Hg + DTT-treated rats was similar. Fractionation of the supernatant on G-75 Sephadex gel revealed no difference in the protein profiles between the Hg- and Hg + DTT-treated groups. It is concluded that DTT administration ameliorates the nephrotoxic effect of prior mercury injection by a more subtle mechanism than redistribution of renal cortical mercury.

Subcellular distribution of mercury in liver of lake trout (Salvelinus namaycush).

Mercury was found primarily (80%) in the submicroscopic material (magnification x<7700) of environmentally exposed adult lake trout from Lake Michigan, USA.

Organ and Subcellular Distribution of Mercury in Rats in the Presence of Cadmium, Zinc, Copper, and Sodium Selenite

AbstractAs environmental exposure is never restricted to a single metal, it is inevitable that research frequently includes the study of interaction between toxic and other metals [1].The simplest conceivable interaction mechanism would be a direct chemical reaction leading to the formation of complex or compound which reduces the biological availability of the element involved. The formation of such compounds could partly explain the protective effect of selenium against mercury [2]. Results of numerous investigations [3-5] have demonstrated that the amounts of selenium administered determine the distribution of inorganic mercury in rats’ tissues. Selenium increases the concentration of mercury in the liver and decreases it in the kidneys. Sodium selenite decreases the content of mercury mainly in the low-molecular proteins both in the kidney and liver and eliminates the stimulating effect of mercury on synthesis of metallothioneinlike proteins in the kidneys [3, 6, 7]. Selenium also decreases the toxici...

Mercury accumulation in kidney lysosomes of proteinuric rats

The purpose of the present study was to determine whether lysosomal accumulation of mercury in the kidney is due to a leakage of protein-bound mercury through the glomerular filtration barrier followed by reabsorption into the lysosomal system of the proximal tubule. The subcellular distribution of mercury in the kidney was studied in four different groups of rats with and without proteinuria: normal young rats, young rats with aminonucleoside nephrosis, old rats with spontaneous proteinuria, and old rats with chronic mercury intoxication and proteinuria. Radioactive mercuric chloride (203HgCl2) was injected s.c. into the rats 72 hours before sacrifice. Cell fractionation experiments were carried out on homogenates of the renal cortex by differential centrifugation. Determination of radioactive mercury in the subcellular fractions revealed that mercury was concentrated in the lysosomal fraction of all rats with proteinuria. In contrast, normal rats without proteinuria had the highest concentration of mercury in the supernatant, and there was no enrichment of mercury in the lysosomal fraction. Gel filtration chromatography performed on urine samples from proteinuric rats demonstrated that excreted mercury in renal lysosomes of proteinuric urine support the hypothesis that mercury bound to plasma proteins passes the glomerular filtration barrier in proteinuric conditions and enters the lysosomal system of the proximal tubule by way of endocytosis.

Subcellular distribution of mercury in the rat kidney cortex after exposure to mercuric chloride

The subcellular distribution of mercury in the rat kidney cortex was studied in tissue fractionation experiments after a single subcutaneous injection of radioactive mercuric chloride ( 203HgCl 2) or following exposure to mercuric chloride in the drinking water (15 mg Hg/liter) for 2, 6, and 10 months. Subcellular fractions were isolated from cortical homogenates by differential centrifugation and assayed for mercury, protein, and acid phosphatase. Seventy-two hours after the injection of 20 μg 203Hg, (specific activity 0.8 mCi/mg Hg), 37% had accumulated in the kidneys. The subcellular distributions of mercury 72 hr after a single injection and after 2 months of exposure via the drinking water were similar, although a significant increase in the relative specific mercury content in the lysosomal fraction was observed after 2 months. The highest concentration of mercury was seen in the supernatant in both groups. After 6 and 10 months of exposure there was an accumulation of mercury in the lysosomal fraction, the relative specific activities being 2.38 and 1.98, respectively. Proteinuria was more pronounced in mercury-treated rats than in controls. In addition, there was a statistically significant increase in kidney weight with increasing time of mercury exposure. The present study demonstrates that mercury becomes concentrated in kidney lysosomes in rats with chronic mercury intoxication, whereas there is no enrichment of mercury in the kidney lysosomes after short-term exposure. A positive correlation between proteinuria and the presence of mercury in renal lysosomes is suggested.

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 203HgCl 2 intravenously at a dose of 0.5 mg Hg/kg, every other day for 2 weeks. Na 2SeO 3 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 metabolism of mercuric chloride.

The distribution of mercury and selenium in subcellular fractions was examined to see effects of selenium on metabolism of mercuric chloride in rats. The subcellular distribution of mercury and selenium was changed greatly with the concurrent administration of them and decreased in soluble fraction and increased in nuclei and debris fractions. We found an interesting result that 56% of mercury existed in soluble fraction with the administration of mercury alone and only 1% of mercury with the concurrent administration of mercury and selenium. In this point, the molar ratio of mercury to selenium was about 1 : 1 in nuclei and debris, mitochondria and microsomes fractions, respectively. Amount of mercury in nuclear fraction prepared by the method of Chanda and others with the concurrent administration of mercury and selenium, was 9 times that with the administration of mercury alone. Furthermore, insoluble nonhistone protein fraction from nuclear fraction had 60% of mercury and in this fraction, amount of mercury per mg protein with the concurrent administration of mercury and selenium was about 13 times that with the administration of mercury alone. The behavior of mercury and selenium was also examined in the plasma. It was considered that mercury and selenium accumulated with the ratio of 1 : 1 in the plasma. We found that the gel filtration pattern of mercury in plasma protein on Sephadex G-200 chromatography was changed greatly and most of mercury was accumulated in some protein of high molecular fraction with the concurrent administration of mercury and selenium.