The distribution of mercury and selenium has been examined in subcellular fractions of rat liver and kidneys in prolonged exposure to HgCl2 and Na2SeO3 administered separately and simultaneously. The molar ratio of mercury and selenium concentrations in subcellular fractions of the organs examined varied considerably. Selenium displaced mercury from the soluble kidney fraction bound mainly with metallothionein to the nonhistone protein fraction of liver nuclei. The Hg-stimulated biosynthesis of metallothionein has been eliminated under the influence of selenium.

No abstract

Sodium selenite was administered to rats before, after, and simultaneously with mercuric chloride. In all animal groups, mercury was administered intravenously in doses of 0.5 mg/kg every other day for two weeks. Selenium was given intragastrically either in a single dose of 7.0 mg Se/kg or in repeated doses of 0.1 mg Se/kg every day for weeks. It was demonstrated that, depending on the administration schedule, selenium induced significant changes in the binding of mercury by soluble fraction proteins both in the kidneys and in the liver. In every exposure, the mercury content decreased mainly in the low-molecular weight proteins, and the level of metallothionein-like proteins was diminished in the both organs. In the kidneys, the mercury content showed a correlation with the level of metallothionein (r=0.78). Amounts of mercury below 10 μg/g kidney do not stimulate metallothionein biosynthesis in this organ. A distinct interaction effect was observed in the case of a simultaneous administration of equimolar amounts of both the metals in question.

The influence of selenium on methylmercury excretion, organ and subcellular distribution, and demethylation was studied in the guinea pig at different times following a single equimolar dose (50 miroM/kg) of CH203 3) HgCl and Na2SeO3 administered separately or concomitantly per os. Excretion of mercury through feces was the dominant clearance pathway in both groups. Selenium significantly decreased excretion of total and organic mercury in feces during the course of the study, but in the urine only on d 13. Selenium also significantly decreased the concentration of total mercury in major organs. The exception was brain on d 1, in which mercury levels were higher in the presence of selenium; however, on d 7 and 13 both cerebrum and cerebellum showed lower mercury levels as compared to the group treated with methylmercury alone. Selenium had no significant effect on the subcellular mercury distribution in the liver, kidney, and cerebrum, other than that which could be accounted for the whole organ uptake. The level of organic mercury in most of the analyzed organs was significantly decreased by the presence of selenium; however, relative proportions of inorganic to organic mercury remain unchanged. The single exception was kidney, where selenium markedly decreased the relative amount of inorganic mercury.

The influence of methylmercury (MeHg) on the tissue and subcellular binding of selenium was determined. Adult female guinea pigs received either 75Se (as sodium selenite) or MeHg (as chloride) followed 5 h later by an equimolar dose of 75Se. Animals were sacrificed 1, 3, 7, and 13 days after administration. Pretreatment with MeHg significantly altered the organ distribution of 75Se, particularly during the first week of the study. 75Se concentrations were markedly reduced in most organs of animals receiving both 75Se and MeHg except the liver, which contained markedly elevated 75Se levels. The subcellular distribution of 75Se was also altered by MeHg. Within liver, kidney and brain, 75Se was primarily bound to nuclear and mitochondrial fractions in both treatment groups, but nuclear binding was higher in animals receiving both compounds. Within nuclear fractions, most 75Se was bound to insoluble-nonhistone proteins. In the presence of MeHg, total nuclear binding of 75Se increased, but total binding to insoluble-nonhistone proteins decreased. MeHg also reduced the total 75Se binding to high molecular weight proteins of the soluble fraction. Alterations in tissue and subcellular binding of MeHg and Se may contribute to the lower degree of toxicity observed in animals receiving both compounds.

Distribution and retention of mercury and selenium was studied in rats exposed repeatedly to HgCl2 injections (0.5 mg Hg/kg to the tail vein every other day) and intragastrically to Na2SeO3 (0.5 mg Se/kg every day), applying combined and separate administration of these metals for 2 weeks. Whole-body retention of mercury in the presence of selenium was augmented by 20% and that of selenium in the presence of mercury by 4% with respect to the administered dose. Combined administration of mercuric chloride and sodium selenite brought about damage to the epithelial cells of renal proximal convolutions and formation of protein casts in their lumen. These changes had the same pattern as those induced by administration of mercuric chloride alone, but the intensity was lower. Submicroscopic studies revealed that repeated combined administration of sodium selenite and mercuric chloride did not completely abolish the mercury-induced mitochondrial swelling and contributed to chromatin destruction in the hepatocyte nuclei.

Inorganic mercury, administered to rats in a single dose of 0.5 mg Hg/kg is accumulated in the kidneys mainly in the soluble (54%) and nuclear (30%) fractions, showing decreasing tendency with time. Mitochondrial and microsomal fractions, initially accumulating approx. 11 and 6% of total Hg, show a tendency to increase the absolute level of Hg for the first week after administration. In the soluble fraction low-molecular weight, metallothioneinlike proteins are mainly responsible for the accumulation of mercury, in other fractions proteins of higher molecular weight prevail.

Distribution and retention of zinc in the presence of cadmium and copper was studied in rats exposed repeatedly to these metals. The experiment was performed on white rats of the Wistar strain. The animals were divided into four groups/five rats each: 1) 65ZnCl2; 2) 65ZnCl2 + CdCl2; 3) 65ZnCl2 + CuCl2; and 4) control group. Rats were administered sc every other day for two weeks: 65ZnCl2-5 mg Zn/kg; CdCl2-0,3 Cd/kg; and CuCl2-2 mg Cu/kg. The zinc content was measured in rat tissues by gamma-counting. Effect of Cd and Cu on subcellular distribution of zinc in the kidney and liver and on the level of metallothionein were also examined. Whole body retention of zinc under the influence of cadmium was lower than that observed in animals treated with zinc alone. However, copper increased twofold the whole body retention of zinc. Cadmium elevated the accumulation of zinc only in the kidneys nuclear fraction and liver soluble fraction. In the kidneys and liver, copper elevated the accumulation of zinc, in the nuclear, mitochondrial, and soluble fractions. The level of metallothionein-like proteins (MT) in the kidneys after a combined supply of zinc and copper was significantly increased with respect to the group of animals treated with zinc alone. These results indicated complex interactions between cadmium, copper, and zinc that can affect the metabolism of each of the metals.