Jadwiga Chmielnicka

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.

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 Na2 75SeO3 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.

Distribution of tin in the rat and disturbances in the metabolism of zinc and copper due to repeated exposure to SnCl2

The effect of stannous chloride on tissue concentrations of zinc and copper was studied in female rats. The animals were subjected to repeated exposure to seven doses given every other day 2 mg Sn/kg, subcutaneously. About 60% of tin 113Sn was retained in the body. Of this amount, about 95% accumulated in the skin and hair. In the remaining organs the tin concentrations corresponded to 2.57 to 0.0001% of the retained dose. In comparison with the control group a 3-fold increase of the content of zinc was found in the liver while a decrease were revealed in the spleen, heart, brain, lungs, and especially in muscle. A statistically significant decrease of the copper content was found in the blood and brain.

The tissue disposition of zinc and copper following repeated administration of cadmium and selenium to rats

Female rats were divided into four groups of five rats each including one control group (C). The animals were administered Na2SeO3 (Se), (CdCl2 Cd), and Na2SeO3 + CdCl2 (Cd + Se). Sodium selenite was given intragastrically at a dose of 0.5 mg Se/kg every day and cadmium chloride was injected subcutaneously every other day at a dose of 0.3 mg Cd/kg for 2 weeks. Exposure of rats to Cd caused an increase in the concentration of copper in the kidneys, blood, and liver and a decrease in the lung, but increased the concentration of zinc in the liver and brain and diminished it in the muscles and bones. In animals exposed to Se an increase in the copper concentration was observed in blood and brain; zinc was increased in the blood, heart, brain, and stomach, but decreased in the kidneys. Exposure of rats to Cd + Se resulted in an increase of copper in the kidneys and a decrease in the spleen, lungs, stomach, muscles and bones. Se prevented the cadmium-induced diminution of the zinc levels in the muscles and bones.

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.

Disturbances in the metabolism of endogenous metals (Zn and Cu) in nickel-exposed rats.

The effect of nickel chloride on tissue concentrations of zinc and copper was studied in female rats. Animals were subjected to repeated exposure to 5 mg Ni/kg. Whole-body retention of zinc increased about 30%, and retention of copper did not change. Increase of the zinc content was observed in liver, but in kidneys, lungs, and brain zinc content decreased. It was also noted that the level of metallothionein was higher in nickel-exposed rat liver than in control rat liver. Concentration of metallothionein was correlated with the metal contents (Ni, Cu, Zn).

Binding of inorganic mercury by subcellular fractions and proteins of rat kidneys

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.ZusammenfassungAnorganisches Quecksilber, Ratten in einer einzelnen Dose von 0,5 mg Hg/kg verabreicht, wurde in den Nieren vorwiegend in der löslichen (54%) und in der Kern-Fraktion (30%) angereichert, und in beiden Fraktionen wurde eine zeitabhängige Abnahme festgestellt. In der mitochondrialen und mikrosomalen Fraktion, in denen zuerst ca. 11 und 6% Quecksilber gefunden wurde, konnte über die erste Woche eine zunehmende Tendenz festgestellt werden. In der löslichen Fraktion waren die metallothionein-ähnlichen Eiweißstoffe von niedrigem Molekulargewicht vorwiegend für die Bindung von Quecksilber verantwortlich. In anderen Zell-Fraktionen war Quecksilber meistens an Eiweiß-stoffe von hohem Molekulargewicht gebunden.

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.