(Copper, zinc)--thionein in pig liver.
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Biomedical subjects
Publications and source records attributed to L Magos.
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The effects of three ligands for ligandin on the biliary excretion of methylmercury were investigated in male rats injected intravenously with 1.0 mg/kg Hg as Me203 HgCl. Bromosulphophthalein and indocyanine green inhibited the biliary excretion of methylmercury, while bilirubin had no such effect. None of the compounds tested which inhibited the biliary excretion of methylmercury decreased bile flow or changed the hepatic concentration of mercury of non-protein thiols. The possibility of the involvement of ligandin in the biliary excretion of methylmercury is discussed.
Methylmercury, after incubation at 3k7 degrees C and pH 7.0 with selenite in the presence of rat erythrocytes, can be extracted into benzene as an unstable 2 : 1 complex with selenium. The same complex, possibly bis-methylmercury selenide, is formed when methylmercury is treated with hydrogen selenide at pH 7.0 in the absence of erythrocytes.
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The kidney uptake of Hg2+ was increased by Cd2+-pretreatment when Hg2+ was given intraperitoneally but not subcutaneously. Subsequent s.c. administration of maleate increased Hg2+ release from the kidneys only if Hg2+ was given subcutaneously. Neither the effect of Cd2+, nor that of maleate, on the distribution of Hg2+ among the renal soluble protein fractions was affected by the route of Hg2+ administration. The protective effect of Cd2+-pretreatment against the nephrotoxic effect of Hg2+ was also independent of the route of Hg2+ administration. Maleate given in nephrotoxic doses removed Hg2+ and copper, but not Cd2+ from the renal metallothionein fraction. Mercury in the urine, however, was not complexed by proteins with the molecular weight of thionein, but was bound to high molecular weight proteins and diffusible molecules. These findings are discussed in relation to the role of metallothionein in the interaction between Cd2+ and Hg2+.
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In phenobarbitone-treated starved male rats 1 g/kg 3-amino-1,2,4-triazole produced moderate liver necorsis and increased the serum glutamic-pyruvic transaminase activity. If half an hour after the administration of aminotriazole animals were exposed for 4 h to 2.0 mg/l CS2, the necrotic damage in the liver was larger and the serum glutamic-pyruvic transaminase activity higher than in rats not exposed to CS2. Carbon-disulphide in phenobarbitone-treated starved male rats caused only a very slight increase in the serum transminase activity in spite of the widespread hydropic degeneration in the liver. These experiments indicated that increase in serum transaminase activity is the consequence of necrosis and not hydropic degeneration; aminotriazole is hepatotoxic in rats when microsomal enzymes are induced and the hepatotoxicity of aminotriazole and carbon disulphide is potentiated by the administration of the other compound.
CBA/J mice injected three days beforehand with 203HgCl2 were given ethanol or water by gavage and placed in a chamber designed to collect exhaled mercury. Ethanol treatment led to an eight-fold increase of counts accumulated on a filter over a four-hour period, compared with water-treated mice. The mercury-collection apparatus tested for extracorporeal contribution of volatilised mercury indicated that the counts originated from the air exhaled by the mice.
The interaction between two metals, which can be either synergistic or antagonistic, implies that the behavior of one is changed by the presence of the other. Possible mechanisms of these interactions, which include chemical association, competition for carriers, metabolic changes, induction of binding proteins, membrane alterations are discussed.
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Twenty-four h after the subcutaneous administration of 0.5 mumoles selenite labelled with 75Se to rats of 200 g body weight, the retention of selenium at the injection site was significantly increased by the presence of equimolar amounts of methylmercury in the injection solution. The retention of Me203HgCl was not affected by the presence of selenite. The most significant shift caused by interaction was a decrease in the blood content and an increase in the brain content of 203Hg. The brain content of 75Se was also increased to a lesser extent. The shift in the distribution--which was the same whether the two metals were injected at the same site or separately--continuously decreased from 6-48 h. The same interaction pattern was observed when methylmercury and selenite were administered by gastric gavage and differences in distribution increased when the dose was increased from 1.25 mumoles/kg to 2.5 mumoles/kg. The increase in the brain content of mercury caused by selenite was not restricted to simultaneous administration and occurred when selenite was given 2-7 days after methylmercury.
The arrhythmogenic effect of 8 microgram/kg noradrenaline given i.v. was increased in male rats pretreated 1-2 days earlier with phenobarbitone and starved from the time of the first phenobarbitone injection (80 mg/kg followed by 50 mg/kg 6 h later). Daily exposure to 4.0 mg/l CS2 (first exposure 24 h after the first phenobarbitone injection) for 4 h prevented the decline in susceptibility on the 3rd and 4th days after phenobarbitone, when the reaction of unexposed rats to noradrenaline returned to normal.
The interaction between three heavy metals, cadmium, mercury and zinc was investigated. The metals were injected subcutaneously into the hind leg of male rats of approximately 200 g body weight in a volume of 0.2 ml either alone or in combination with another metal. It has been shown that interaction started at the site of injection, at which the retention of one metal was increased by the presence of the other over a 48 h period. Besides this local interaction, probably based on competition for a carrier compound, there were differences in distribution. Analysis of the data indicates that metals injected simultaneously can influence the distribution of each other and, although each of the studied metal is able to induce thionein, the observed interactions cannot be explained by a single mechanism.
Forty-eight hours after the simultaneous administration of either 1.8 mumoles Se (as Na2SeO3) to 200 g male rats with equivalent doses of Cd (as CdCl2) or 0.5 mumoles Se with equivalent doses of Hg (as HgCl2) the retention of selenium at the subcutaneous injection site was affected only when it was given in a single injection with the heavy metal. The retention of cadmium was increased only if selenium was injected separately and the retention of mercury was increased both in single and separate injections. When there was an increase in retention at the site of injection, this made up less than 8% of the dose for selenium and mercury and 3% for cadmium and thus could not explain either changes in distribution or the reported protective effects by one metal against the other. The shift in the distributionpattern of one metal caused by the other metal was similar, and independent of whether they were injected in single or separate injections. However the shift in the distribution of interacting metals showed some differences indicating that interaction could not be mediated through the formation of a stable complex between selenium on the one hand and mercury or cadmium on the other.
Female rats (65-75 days old) were given orally 0.84 or 3.36 mg Hg/kg as methylmercury chloride (MeHgCl) 5 times a week for 13 and 3 weeks, respectively. The proportion of inorganic to total mercury remained as low as 6% in whole animal though it increased to above 40% in the kidneys. Differences in organ half times and the negative correlation with time for blood to liver, brain and kidney mercury ratios indicated more than one compartment for MeHg+. Brain had 26 days half time with a 32% final equilibrium concentration in relation to the body concentrations. Brain concentrations of mercury reported on rats dosed repeatedly with MeHg+ agreed with these values which justifies their use when experiments are planned to give a certain brain MeHg+ concentration. Half time for the whole body was 34 days but patholgical changes-weight loss, tubular damage, slow gastrointestinal passage-disturbed the accumulation curves in the higher dose group. Blood to kidney ratio and uptake of MeHg+ by kidneys also changed significantly.
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