Mercury animal models

In animal models, dimercaprol prevents and reverses arsenic-induced inhibition of sulfhydryl-containing enzymes and, if given soon after exposure, may protect against the lethal effects of inorganic and organic arsenicals. Human data indicate that it can increase the rate of excretion of arsenic and lead and may offer therapeutic benefit in the treatment of acute intoxication by arsenic, lead, and mercury. 

Dimercaprol is FDA-approved as single-agent treatment of acute poisoning by arsenic and inorganic mercury and for the treatment of severe lead poisoning when used in conjunction with edetate calcium disodium (EDTA see below). Although studies of its metabolism in humans are limited, intramuscularly administered dimercaprol appears to be readily absorbed, metabolized, and excreted by the kidney within 4-8 hours. Animal models indicate that it may also undergo biliary excretion, but the role of this excretory route in humans and other details of its biotransformation are uncertain. 

Of particular importance is the collection of pharmacokinetic data showing the relationship between low-level exposure (acute, intermediate, and chronic) and blood and urine levels throughout the study. duration. Also tissue levels at necropsy should be taken immediately after cessation of dosing. In animal studies, a similar group of animals should be followed for urine (and blood, but not as important here) mercury levels for periods of 30, 60, 90, and 120 days postdosing to examine whole-body excretion, and necropsy tissue samples should also be taken from several animals at 30, 60, 90, and 120 days postdosing. Primates would be the best animal model, but rodent models could suffice. 

Bigazzi PE. 1992. Lessons from animal models The scope of mercury-induced autoimmunity. Clin Immunol Immunopathol 65(2) 81-84. 

There is some evidence, either in animal models or following human exposure, that several pesticides used currently or in the recent past can cause slight changes that could be interpreted as autoimmune-like effects . However, data supporting this hypothesis are scarce. In some cases, the mere inclusion of observed changes as indicative of autoimmunity is even questionable, whereas in other cases, results of one study have not been confirmed by a subsequent study. Only few compounds that are no longer in use today (i.e. mercury derivatives, hexachlorobenzene) have been... 

B. Succimer is protective against the acute lethal and nephrotoxic effects of mercuric salts in animal models, and increases urinary mercury excretion in animals and humans. It may therefore have clinical utility in the treatment of human poisoning by inorganic mercury. 

A. Unithlol has been used primarily In the treatment of Intoxication by mercury, arsenic, and lead. In animal models, unithlol has averted or reduced acute toxic effects of inorganic mercury salts and Inorganic arsenic when administered promptly (minutes to hours) after exposure. Unithlol Is associated with a... 

VI. Dosage and method of administration. Unithiol may be administered by oral. Intramuscular, or intravenous routes. The intravenous route should be reserved for treatment of severe acute intoxication by inorganic mercury salts or arsenic where compromised gastrointestinal or cardiovascular status may interfere with rapid or efficient absorption from the gastrointestinal tract. In animal models, oral unithiol did not increase the gastrointestinal absorption of mercuric chloride. 

Lyons TJ, Christu CN, Larsen FS (1975) Ammoniated mercury ointment and the nephrotic syndrome. Minn Med 58 383-384 Maibach H, Boisits E (eds) (1982) Neonatal skin structure and function. Marcel Dekker, New York Marshall JD, Schneider RP (1977) Systemic argyria secondary to topical silver nitrate. Arch Dermatol 113 1077-1079 Marzulli F, Maibach H (1975) Relevance of animal models the hexachlorophene story. In Maibach H (ed) Animal models in dermatology. Churchill Livingstone, Edinburgh, pp 156-167 Marzulli F, Maibach H (eds) (1996). Dermatoxicology, 5th edn. Hemisphere, Washington... 

Previous reports showed an increase of SLE cases in residential areas situated near industrial sites or in places with severe environmental contamination. In particular, pollution caused by high concentrations of oil field waste, pristane, mercury and phytane seems to be associated with higher risk of developing SLE for the general population. Pristane has already been used in animal models to demonstrate the induction of autoantibodies and clinical features similar to human SLE. ... 

In experiments with the perfused guinea pig placenta Kelman (1979) has studied the transfer of heavy metals from the maternal to the embryonic circulation. Using this animal model he was able to demonstrate that the placental transfer for methylmercury was 10-times higher than for anorganic mercury. 

Further development of PBPK/PBPD models will assist in addressing these differences and in extrapolating animal data to support risk assessments for mercury exposure in humans. 

Carrier G, Brunet RC, Caza M and Bouchard M (2001) A toxicokinetic model for predicting the tissue distribution and elimination of organic and inorganic mercury following exposure to methyl mercury in animals and humans. 1. Development and validation of the modd using experimental data in rats. Toxicol Appl Pharmacol 171 38-49. 

Several strategies for the phytoremediation of arsenic and mercury pollution, tising bacterial, animal, and plant genes, have been tested in model... 

Of all turnover rates in the human body, the total excretion rate seems to be the lowest. This means that the body can be looked upon as a one-compartment system in which the intake is balanced by the excretion. In 1968 (Berglund and Berlin, 1969), we therefore proposed a model for the mercury accumulation in the human body, a model which has been widely used (see Fig. 8). However, it may be pointed out that this model is an approximation and valid pnly at non-toxic dose le vels. The indications from animal experiments are that at increasing dose levels the elimination rate goes down. Close to toxic blood levels the brain shows an increasing tendency to accumulate methyl mer-... 

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