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Biomedical subjects

L Magos

Publications and source records attributed to L Magos.

At least 73 records · Page 4Linked to original sources

The interaction between cadmium, mercury and zinc--administered subcutaneously in a single injection.

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.

Animals↗

Differences in distribution and excretion of selenium and cadmium or mercury after their simultaneous administration subcutaneously in equimolar doses.

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.

Animals↗

The kinetics of methylmercury administered repeatedly to rats.

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.

Administration, Oral↗

Effects of diethyldithiocarbamate on the catabolism of tyrosine in the rat brain.

500 mg/kg sodium diethyldithiocarbamate (DDC) and trace quantities of uniformly labelled 14C-tyrosine were administered simultaneously to male albino rats of Porton-Wistar strain of approximately 210 g body weight. Thirty minutes later total radioactivity, the concentration and the specific activity of free tyrosine were increased both in plasma and in the brain by 40% compared with rats untreated with DDC. The incorporation of 14C from 14C-tyrosine into the fraction corresponding to the elution of glutamine-glutamate from the amberlite resin column was 80% less in the brain 30 min after DDC. The exhalation of 14CO2 was depressed by 80% in the first hour after DDC. When 14C-tyrosine was given 3.5 h after DDC the only differences between experimental and control rats were the increased incorporation of 14C into the glutamine-glutamate and aspartate fractions and the increased exhalation of 14CO2 which became significiant in the third and fourth half hour periods after the injection of 14C-tyrosine. From the experiments it is concluded that DDC, an inhibitor of dopamine-beta-hydroxylase, also interferes with the major catabolic pathway of tyrosine.

Animals↗

The effect of oral doses of a polythiol resin on the excretion of methylmercury in mice treated with cysteine, D-penicillamine or phenobarbitone.

Mice dosed with methylmercury chloride (0.5 to 2.0 mg Hg/kg i.p.) labeled with the 203Hg isotope were given polythiol resin in their food (2% w/w). The effect of pretreatment with phenobarbitone, or co-administration of D-penicillamine or L-cysteine, was tested on the efficacy of the resin to accelerate the excretion of methylmercury. The effect of the polythiol resin in enhancing fecal excretion was dependent on the dose of methylmercury, it being significantly greater at doses of 1.0 and 2.0 than at 0.5 mg Hg/kg. In animals given the resin and phenobarbitone (0.1% w/w drinking water), fecal excretion was approx. 36% greater than in animals given resin alone. Penicillamine (2.5 mg/ml drinking water) actually retarted elimination of methylmercury in animals given the resin. Despite the enhanced efficacy of the resin plus phenobarbitone, the brain levels of methylmercury were not reduced beyond those seen in animals given resin alone. The mechanisms and implications of these effects are discussed.

Animals↗

Cadmium-thionein and the protection by cadmium against the nephrotoxicity of mercury.

Uptake of Hg2+ into the renal and hepatic metallothioneins of rats is increased by pretreatment with Cd2+. This increased uptake occurs both by displacement of Cd2+ (and of Zn2+) from the presynthesized cadmium-thionein, and by further synthesis of thionein. The former mechanism predominates in the kidney of the male rat, which is more sensitive than the female to Hg2+. The latter mechanism, which occurs particularly in the kidney of the female, also is considered to involve an initial displacement of Cd2+ from cadmium-thionein, but is followed by further synthesis of the metalloprotein, which is induced by the liberated cation. Pretreatment with Cd2+ increases not only the incorporation of Hg2+ into the renal metallothionein, but also the uptake of Hg2+ into other components of the kidney. At dose levels of Hg2+ at which Cd2+-pretreatment gives complete protection against the nephrotoxicity in male and female rats, the increase in Hg2+-uptake into both the particulate components and into the soluble fraction of the kidney is greater than into metallothionein. It is concluded, therefore, that binding of Hg2+ by pre-induced cadmium-thionein alone cannot explain the protection by Cd2+ against the nephrotoxicity of Hg2+.

Animals↗

A radioactive mercury vapor generating and exposing system for small scale animal experiments.

An apparatus is described for exposing small animals to high specific activity elemental mercury vapor. The vapor is generated by reduction of mercury chloride labelled with the 203HG isotope. The vapor is carried by a constant stream of air into the exposure chamber. The method has been used to expose rats or mice to constant air concentrations of mercury vapor in the range from 0.008 to 0.32 mg/m3. The specific activity of the mercuric chloride used in the study was approximately 1.8 mCi/mgHg. This is sufficiently high to allow measurement of tissue deposition of mercury after an exposure period of only 30 minutes.

Animals↗

The effects of dimercaptosuccinic acid on the excretion and distribution of mercury in rats and mice treated with mercuric chloride and methylmercury chloride.

1 All five rats in a group survived if dimercaptosuccinic acid (DMSA), a water soluble derivative of 2,3-dimercaptopropanol (BAL), was given in doses of 10-40 mg/kg intraperitoneally 30 min, 4 and 24 h after administration of 2.4 mg/kg Hg as HgCl2, whereas three out of a group of five died if DMSA was not given. DMSA 20 mg/kg increased urinary excretion and decreased the body burden significantly more than 10 mg/kg DMSA, but further doubling of the dose had only marginal effects. 2 DMSA was able to reduce body burden and increase urinary excretion of Hg when intraperitoneal treatment started eight days after the subcutaneous administration of HgCl2. 3 DMSA was effective in decreasing body burden and the brain concentration of Hg in rats dosed orally with methylmercury (MeHgCl) when intraperitoneal treatment started with 40 mg/kg DMSA 24 h after Hg. Increase in the urinary excretion of mercury was responsible for the decrease in body burden. 4 DMSA was effective when given in the drinking water of rats or mice both against inorganic Hg and MeHgCl. In mice treated intraperitoneally with MeHgCl, DMSA 19.5 mug/ml in the drinking water caused a significant decrease in the body burden and increase in the excretion of Hg. 5 DMSA was about four times more efficient than D-penicillamine in decreasing the body burden of Hg. As their toxicity is in the same range, the higher efficiency of DMSA offers a larger margin of safety for the mobilization of Hg.

Animals↗

Tissue levels of mercury in autopsy specimens of liver and kidney.

Fifty-one autopsy specimens of liver were analysed for total mercury. Thirteen specimens contained less than 10 mg/kg of mercury, with a minimum value of 1.4 mg/kg, indicating that death in suspected cases was not always due to lethal exposure to methylmercury. The methylmercury concentration in 28 livers was 10-30 mg/kg. Limited additional estimations have shown that 71% of the liver mercury was organic and that the level of mercury in the liver of a 7-month-old fetus was only 25% of that in the liver of the mother. In a patient who died in hospital with a blood mercury level of 4.1 mug/ml, the liver contained 16.5 mg/kg of mercury.Differences between these results and those found in the outbreak of methylmercury poisoning in Japan are discussed. Any extrapolation of tissue mercury levels in relation to the toxic effects of methylmercury must take account of the intensity and duration of exposure.

Adolescent↗