Toxicity
of lead
1.
Characteristics
2. Lead poisoning
3. Action Mechanism
4. Neurotoxicity
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Lead
is the eighty-second element in the periodic table. Its atomic number
is 82 and its atomic weight 207.19. Lead has been known since ancient
times and is relatively abundant in the earth's crust (13 g/ton,
ranking 36th), where it is found in galena (PbS). The lead crystal has
a cubic structure with centred faces. Lead is a lustrous, bluish metal;
it is relatively soft, extremely malleable and ductile and is a poor
conductor of electricity. It is highly resistant to corrosion but
oxidises and blackens when it comes into contact with air. Lead piping
bearing the insignia of the Roman Empire, once used for sewerage
plumbing, can still be found. |
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Lead ranks second in the
list of prioritised hazardous substances issued by the U.S. ATSDR
(Agency for Toxic Substances and Disease Registry) in 1999. The noxious
effects of this metal have long been well known, especially as regards
acute forms of poisoning. However, as for many other contaminants, the
threshold level of safety has been drastically lowered recently. Until
approximately 30 years ago, chronic lead poisoning was defined by blood
lead levels above 80(gr/dl, while today a lead level of 30(gr/dl in
blood is considered excessive and levels at or above 10(gr/dl (0.1
ppm) are considered potentially harmful, particularly in children.
The
presence of lead in the blood stream (inside the red blood cells and
mostly linked to haemoglobin) provokes anaemia. This disease cannot be
considered a symptom, but rather a delayed sign of lead poisoning.
Through the blood, lead reaches all other tissues. Because of its
capacity to "mimic" calcium (see mechanisms), lead is stored in the
bones and becomes a stable bone component, particularly in the case of
insufficient calcium intake. This lead deposit may be mobilised and
return into the blood stream under particular states of physiological
stress (pregnancy, breast-feeding, diseases), but also as a consequence
of greater calcium intake in the diet. This stable presence of lead in
bones makes recovery from lead poisoning extremely slow, even when the
toxic agent has been completely eliminated. |
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Lead's toxicity is largely due to its capacity to mimic
calcium1 and substitute it in many of the fundamental cellular processes that depend on calcium. |
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Lead uptake through the blood-brain
barrier2
and into the brain proceeds at an appreciable rate, consistent with its
action as a potent central neurotoxin. The transport mechanism is not
totally understood, but it most likely involves passive uptake of PbOH+
ions. In the brain, lead accumulates in astroglia cells3,
which function as a lead sink, protecting the more vulnerable neurons.
On the other hand, astrocytes may be vulnerable to the toxic effects of
Pb2+. Both in astroglia cells and in neurons lead uptake is mediated by
calcium channels. |
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Lead and Calcium
- The chemical basis for lead mimicking calcium is not obvious. Neither
the electronic structures nor the ionic radii of the two elements are
particularly close. Lead has a broader coordination chemistry than
calcium; the latter prefers oxygen ligands, whereas lead will also
complex with other ligands, especially the sulphydryl group, and forms
complex ions with OH-, Cl-, NO3- and CO3 2-. |
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Blood-brain barrier
- The blood-brain barrier is a system of tightly-joined endothelial
cells that form a transport barrier for certain substances between the
cerebral capillaries and the brain tissue. Under these conditions,
solutes may gain access to brain interstitium via only one of two
pathways: (i) lipid-mediated transport, which is restricted to small
molecules (with a molecular weight less than a threshold of
approximately 700 Da) and generally proportional to the lipid
solubility of the molecule or (ii) catalyzed transport, that is by
carrier-mediated or receptor-mediated transport processes. |
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Astroglia cells or Astrocytes - Neuroglia are the non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain and blood-retina barriers, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Astrocytes (from "star" cells) are the largest and most numerous neuroglial cells in the brain and spinal cord. They have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signalling (as in many other functions) is not well understood. |
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