Elżbieta Komsta-Szumska

Binding of mercury and selenium in subcellular fractions of rat liver and kidneys following separate and joint administration.

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.ZusammenfassungDie Verteilung von Quecksilber und Selen wurde in zellfreien Fraktionen von Rattenleber und -nieren untersucht, nachdem getrennt oder zugleich HgCl2 bzw. Na2SeO3 zwei Wochen lang (0,5 mg Hg/kg jeden zweiten Tag i.V., 0,5 mg Se/kg jeden Tag per os, molares Verhältnis l ∶ 5) verabreicht worden waren. Das molare Verhältnis der Hgund Se-Konzentrationen schwankte in den zellfreien Fraktionen der untersuchten Organe beträchtlich. Selen verdrängte Quecksilber aus der löslichen Nierenfraktion. Quecksilber war hauptsächlich mit Metallothionein an die histonfreie Eiweißfraktion der Leberzellkerne gebunden. Unter dem Einfluß von Selen wurde die Hg-stimulierte Biosynthese von Metallothionein unterbunden.

Demethylation and excretion of methyl mercury by the guinea pig

Female guinea pigs were dosed po with 1.0 mg CH3 203Hg/kg as methylmercuric chloride, 10 times over a 3-week period. Tissue distribution, excretion, and accumulation of inorganic and organic mercury were studied. The highest concentration of mercury was found in the kidney. The greatest decreases of mercury levels were observed in the small bowel, red blood cells, liver, and cerebrum. The half-life of whole body clearance, based on a single compartment model, was 31.6 days. Mercury in the kidney, liver, and cerebrum was bound mainly by nuclear and soluble fractions. The highest ratio of inorganic to total mercury was seen in the kidney, 60% of this being as inorganic mercury. Excretion of mercury in the feces was measured throughout the experiment. The relationship of organic to inorganic mercury was relatively constant at about 1:3. Data on the effects of methyl mercury on tissue concentrations of zinc and copper show that the only change in the copper content was a marked increase in the kidney.

Effect of selenium on distribution, demethylation, and excretion of methylmercury by the guinea pig

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.

Effect of interaction between 65Zn, mercury and selenium in rats (retention, metallothionein, endogenous copper)

Interaction of zinc with mercuric chloride and sodium selenite was studied in the rat at the organ and subcellular levels (liver and kidneys). Zinc chloride was administered subcutaneously at dose of 5 mg Zn/kg, mercury chloride into the tail vein at a dose of 0.5 mg Hg/kg (both metals every other day during 2 weeks) and sodium selenite intragastrically, at doses of 0.1 mg Se/kg, every day. Zinc retention in the rat did not exceed 20% and was unchanged in the presence of mercury. An interaction effect was reflected by an increased whole-body retention of zinc by selenium, mercury, and selenium. In the presence of selenium no peak of metallothionein-like proteins stimulated by zinc or mercury was found in the soluble fraction of the kidneys. The metallothionein level did not differ from that typical for control group animals, too. A significant increase in the level of endogenous copper was found only in the kidneys of rats exposed to zinc in the presence of mercury and selenium.

The effect of methylmercury on the distribution and excretion of selenium by the guinea pig.

The influence of methylmercury (MeHg) on the tissue and subcellular binding of selenium was determined. Adult female guinea pigs received either75Se (as sodium selenite) or MeHg (as chloride) followed 5 h later by an equimolar dose of75Se. Animals were sacrificed 1,3,7, and 13 days after administration. Pretreatment with MeHg significantly altered the organ distribution of75Se, particularly during the first week of the study.75Se concentrations were markedly reduced in most organs of animals receiving both75Se and MeHg except the liver, which contained markedly elevated75Se levels. The subcellular distribution of75Se 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, most75Se was bound to insoluble-nonhistone proteins. In the presence of MeHg, total nuclear binding of75Se increased, but total binding to insoluble-non-histone proteins decreased. MeHg also reduced the total75Se 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.

Whole-body retention of mercury and selenium and histopathological and morphological studies of kidneys and liver of rats exposed repeatedly to mercuric chloride and sodium selenite

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.

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

Abstract Sodium selenite was administered to rats employing different sequence patterns: before, after, and simultaneously with mercuric chloride. All animal groups were given 203 HgCl 2 intravenously at a dose of 0.5 mg Hg/kg, every other day for 2 weeks. Na 2 SeO 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.

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...

Variation of the level of mercury and metallothionein in the kidneys and liver of rats with time of exposure to sodium selenite

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.

Activity of glutamate and malate dehydrogenases in liver and kidneys of rats subjected to multiple exposures of mercuric chloride and sodium selenite

Rats were subjected for 2 weeks to separate and combined exposures to mercuric chloride and sodium selenite at doses of 0.5 mg Hg/kg and 0.5 mg Se/kg. The content of mercury, selenium and protein as well as the activities of glutamate dehydrogenase (GLDH) and malate dehydrogenase (MDH) were determined in homogenates, mitochondria and intramitochondrial structures of the exposed animals. It was found that both separate and combined exposures of rats to mercuric chloride and sodium selenite inhibited GLDH activity and did not affect MDH activity in the examined organs. Mercury-selenium interaction brought about a decrease in the content of mercury in the intramitochondrial structures of kidneys and an increased accumulation of both elements in the outer and inner membranes of liver mitochondria. The biochemical mechanism of mercury-selenium interaction is discussed.