Elemental mercury metabolism

Dimercaprol is FDA-approved as single-agent treatment of acute poisoning by arsenic and inorganic or elemental 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. 

Elemental mercury vapor can enter the body through inhalation and be carried by the bloodstream to the brain, where it penetrates the blood-brain barrier. It disrupts metabolic processes in the brain causing tremor and psychopathological symptoms such as insomnia, shyness, depression, and irritability. Divalent ionic mercury, Hg +, damages the kidney. Organometallic mercury compounds such as dimethylmercury, Hg(CH3)2, are also very toxic. 

The element mercury, also known as quicksilver (symbol Hg for hydrargyrum), and its compounds have no known normal metabolic function. Their presence in the cells of living organisms represents contamination from natural and anthropogenic sources all such contamination must be regarded as undesirable and potentially hazardous. Accumulation of mercury in tissues is reportedly associated with an excess risk of myocardial infarction, increased risk of death from coronary heart disease and cardiovascular disease, and accelerated progression of carotid atherosclerosis. 

This chapter primarily describes the most recent findings on the mechanisms of toxicity and metabolism of methyl, mercuric, and elemental mercury. Since methylmercury is known as one of the most important mercurials to which the general population is frequently exposed in the environment by food consumption, the mechanisms of its toxicity and disposition are discussed in detail. 

The importance of toxic elements in environmental chemistry is rarely questioned, but a relatively small number of elements (mercury, lead, and cadmium) have received a large share of researchers attention. The environmental chemistry of the transition metals, e.g., chromium, nickel, manganese, cobalt, copper, etc., has also been investigated principally because of their roles in metabolism, especially enzymatic processes. However, two non-metals, arsenic and selenium, and two metals, beryllium and vanadium, are elements which will become more significant in the future from environmental and toxicological points of view. Arsenic and selenium have been investigated, but much more work is needed because of the importance of these two elements in the environment. The author considers beryllium and vanadium to be problem metals of the future . The primary exposure route for both beryllium and vanadium is via the atmosphere and as lower environmental standards are imposed, more uses are found for each element, and more fossil fuels (source of V) are burned, the amounts added to the atmosphere will have more significance. 

Mendeleev, Dimitri, 104,107 Mendelevium, oxidation number, 414 Mercuric perchlorate, 237 Mercurous perchlorate, 237 Mercury, oxidation numbers, 414 Mercury (planet), data on, 444 Metabolism, oxidative, 429 Metallic alloys, 309 bond, 303 elements. 303 radius, 380 substances, 81 Metals alkali, 94... 

Not all agents can be readily metabolized. The toxic metals lead and mercury are elements that cannot be degraded but must still be removed from the body. Another important mechanism of detoxification is the attachment or binding of another compound to a toxic chemical to make it easier for the kidney to filter the compound out of the blood and excrete it in the urine. A primary purpose of the kidney is to screen the blood for waste products and concentrate them in the urine for excretion, as occurs, for example, with mercury. Caffeine is excreted in the urine at approximately the same concentration as the blood because the kidney cannot concentrate caffeine. Vitamins, however, are readily concentrated and excess quickly eliminated in the urine. 

We have seen (Section 56.1.13.2.2) that cadmium can induce the synthesis of a Cd-binding protein in fact, the administration of copper, zinc, cadmium or mercury to animals induces the synthesis of these proteins called metallothioneins, which play an important role in the metabolism of these elements. 

Interactions Overabundance of one trace element can interfere with the metabolic use of another element available at normal levels. For example, addition of large amounts of zinc to a diet interferes with (antagonizes) intestinal copper absorption, resulting in copper deficiency from a diet with adequate copper content. Copper deficiency can provoke iron deficiency and anaemia. Molybdenum deficiency in animals can be induced by co-administration of large amounts of the similar element tungsten. Iron deficiency can also increase retention of cadmium and lead, and selenium has been proposed to protect against cadmium and mercury toxicity. 

Hall LL, Allen PV, Fisher HL, et al. 1994. The kinetics of intravenously-administered inorganic mercury in humans. In Kinetic Models ofTrace Elements and Mineral Metabolism During Development, K.M.S. Subramanian and M.E. Wastney, Ed. CRC Press, Boca Raton, FL. p. 1-21. 

The association between metal exposure and renal failure can be approached from two points of view. On the one hand environmental/industrial exposure to heavy metals, more particularly, lead, cadmium and mercury and other inorganic substances such as silicon has been linked to a reduced renal function and/or the development of acute or chronic renal failure [1]. This issue has been dealt with in other chapters of this book. On the other hand patients with chronic renal failure, especially those treated by dialysis are at an increased risk for trace element disturbances (Figure 1). Indeed in these subjects the reduced renal function, the presence of proteinuria, metabolic alterations associated with renal insufficiency, the dialysis treatment, medication etc. all may contribute to either accumulation or deficiency of trace metals. With regard to aluminum intensive research on the element s toxic effects has been performed in the past. Recently, new metal-containing medications have been introduced of which the potential toxic effects should be considered and put in a justified context. 

Metallothioneins are a unique and widely distributed group of proteins. They are characterized by their low molecular weight (—6000), high cysteinyl content, and the ability to bind substantial numbers of metal ions (43). The proteins bind copper and zinc, thereby providing a mobile pool as part of the normal metabolism of these elements, and offer protection from the invasion of inorganic forms of the toxic elements cadmium, lead, and mercury. In addition, other metals, such as iron and cobalt, can be induced to bind. XAS is ideally suited to probe the environment of these different metal atoms (see Fig. 1), and the structural interpretations obtained from an analysis of the EXAFS data obtained in several such studies are summarized in Table 1(44). Thus, in each case, the data are consistent with the primary coordination of the metal deriving from the cysteinyl residues. 

The chemistry of metals, i.e., their behavior as atoms or ions, is a fundamental factor in electrochemical reactions, as well as in the metabolism of plants and animals, where many have essential nutrient and other biochemical functions. Among these are iron, copper, cobalt, potassium, and sodium, often in traces. Some metals are quite toxic, especially cadmium, mercury, lead, barium, chromium, and beryllium, both in elemental form and as compounds. 

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