Sodium maleate-induced potentiation of the penicillamine effect on the urinary mercury excretion.
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Biomedical subjects
Publications and source records attributed to L Magos.
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1. This paper describes an attempt to learn more about the binding of Hg(2+) to tissues at pharmacological concentrations of this metal. Other methods were not applicable to such low concentrations of mercury. 2. The method involved equilibrium dialysis of Hg(2+) against 1% homogenates of rat kidney or liver in the presence of penicillamine. Two classes of mercury-binding sites were observed, one class having a chemical affinity for mercury 100-fold greater than the other class. The binding capacities of the class of higher and lower affinity were respectively 1.0x10(-7) and 30x10(-7)mole of mercury/g. wet wt. of tissue. The same classes of binding sites were found in both liver and kidney homogenates. 3. The binding sites of both classes reacted with only one valency of Hg(2+), the other valency forming a bond with penicillamine. Thus the total binding capacities of both classes are equivalent to 50% of the total reactive protein-bound thiol groups in the homogenate. 4. The results eliminate three possible mechanisms for the preferential accumulation of mercury by kidney. They support the idea that the permeability changes in kidney cells resulting in diuresis are similar to the permeability changes produced on the membranes of other mammalian cell species by mercury.
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The decomposition rate of organomercurials and the potency of the blood-brain barrier increase with the size of the organic radical. Thus methylmercury damages the brain more than thimerosal does, and when intake limits set for methylmercury are applied to thimerosal the safety margin is increased even if the clearances were the same. However, the clearance half-time of ethylmercury in adults is about one-third of the 50 days' clearance half-time of methylmercury given for 60 kg body weight. Moreover, because metabolic rates (e.g. basal metabolism, daily loss of mercury in per cent of body burden) in different weight groups are related to the fractional power of body weight (rule of allometry), mercury clears from the infant body faster than from the adult body. Blood mercury concentrations observed after vaccination showed agreement with allometrically extrapolated concentrations.
A male subject, after exposure to mercury metal at work in 1968, developed classical signs of mercurialism from which he made a slow clinical recovery. He subsequently developed psychoneurotic symptoms and became an alcoholic; he never returned to work and died in 1984. No histological changes relevant to mercury intoxication were found in the brain, but staining by Danscher & Schroeder's method for mercury showed many positively staining lysosomal dense bodies in a large proportion of nerve cells, and the presence of mercury was confirmed by elemental X-ray analysis. The mercury content of the brain was increased, much of it being present in colloidal form.
In the rat the first clinical signs of methylmercury intoxication is loss of appetite, which can be restored by the administration of dimercaptosuccinic acid (DMSA). In female rats which lost body weight as a result of methylmercury treatment, the anorexic effect of methylmercury was reversed even when DMSA was given in the drinking water. When intoxicated animals had the choice between DMSA supplemented water (2.5 mg DMSA/ml) and tap water, they preferred DMSA. This preference is related to the severity of intoxication and is abolished after one or two days. During this time the urinary mercury excretion is substantially increased and the body burden of methylmercury is decreased. The effect of methylmercury mobilization is fast, and can be detected in urine collected from cannulated ureters shortly after the IV administration of 10 or 20 mg/kg dimercaptosuccinic acid.