Chemistry Reference
In-Depth Information
Today the predominant if not the sole source of methylmercury is derived from the methylation of inorganic
mercury in aquatic sediments and soils. Methylmercury is well absorbed from the diet and distributes within a few
days to all tissues in the body. It is present in the body as water-soluble complexes mainly, if not exclusively,
attached to the sulfur atom of thiol ligands, and crosses the blood
brain barrier without hindrance, entering the
e
endothelial cells of the blood
brain barrier as a complex with L-cysteine. The principal target tissue of MeHg is
the brain, and its major toxic effects are on the central nervous system. Whereas adult poisoning affects the visual
cortex and the cerebellum, in neonatal infants the outcome can be much more serious, ranging in its effects from
cerebral palsy to developmental retardation.
Ethylmercury (EtHg) is used in the form of thimerosal as a preservative in vaccines given to children. In recent
years, there has been concern that EtHg exposure may induce neurodevelopmental disabilities such as language
delay and attention deficit-hyperactivity disorder, but especially autism spectrum disorder. It has been removed
from most vaccines in the USA and Europe; but is still used in some developing countries.
Elemental mercury (Hg
) is a naturally occurring form of the metal that exists uniquely in liquid form at room
temperature and quickly turns to vapour when heated. The natural sources of Hg
in the environment include the
release of Hg gases from volcanic eruptions and the erosion of ores that contain Hg. Several studies over the past
30 years have demonstrated that dental amalgam filling releases mercury vapour into the oral cavity. Mouth
breathing carries the vapour to the lung where it is absorbed and distributed to tissues.
Inorganic Hg (I-Hg) compounds (mercury salts) are also a significant source of Hg intoxication in some
countries. Inorganic Hg has been used for many years in numerous products, including various medications,
germicidal soaps, teething powders, and skin creams, many of which are still in use today. Some skin cream
contains as much as 6
e
10% mercurial chloride or calomel.
In the CNS, MeHg accumulates, particularly in astrocytes. Astrocytic swelling, excitatory amino acid (EAA)
release, and uptake inhibition, as well as EAA transporter expression inhibition are known consequences of MeHg
exposure. One fairly obvious way in which Hg
2
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could alter protein functions is by reacting with sulfhydryl
groups, thereby inhibiting enzymes containing reactive thiols groups in or near their active site. Potentially of
greater importance is the observation that dietary selenium (Se) status is inversely related to vulnerability to
methylmercury (MeHg) toxicity. Recent studies have shown that Se-enriched diets not only prevent MeHg toxicity
but can also rapidly reverse some of its most severe symptoms. It is now understood that MeHg is a highly specific,
irreversible inhibitor of Se-dependent enzymes (selenoenzymes). Selenoenzymes, in particular glutathione per-
oxidasen thioredoxin reductase and thioredoxin glutathione reductase, are required to prevent and reverse
oxidative damage throughout the body, particularly in the brain and neuroendocrine tissues. Inhibition of sele-
noenzyme activities in these vulnerable tissues appears to be the proximal cause of the pathological effects known
to accompany MeHg toxicity (
Figure 23.4
). Because Hg's binding affinities for Se are up to a million times higher
than for sulfur, its second-best binding partner, MeHg inexorably sequesters Se, directly impairing selenoenzyme
activities and their synthesis (
Figure 23.5
)
.
e
LEAD
Chronic lead poisoning (saturnism
6
) is a major cause of environmental concern in all countries worldwide. Lead
toxicity affects several organ systems, including the nervous, haematopoietic, renal, endocrine, and skeletal. The
effect of major concern is the impairment of cognition and behaviour during nervous system development in
infants and young children, and the growing body of evidence that exposures to lead in early life may cause
neurodegeneration in later life. Low-level exposure to lead from various environmental sources, including lead-
based paint, and household dust from surfaces covered with such paints, as well as lead in air, food, and water can
6. Saturn was the alchemist's name for lead. The metal Pb (Latin plumbum) was used in domestic plumbing from Roman times on account of
it being soft and malleable. Plumbers (lead workers) nowadays rarely use lead, since most modern houses have water pipes in other metals or
in plastic. The attraction of lead for young children is that it has a very sweet taste.
