Lead 2
Environmental Chemicals

Author: Gianpiero Pescarmona
Date: 07/10/2007


Lead poisoning reduces haeme synthesis

In addition to ALAD genotype, other factors to consider in determining overall susceptibility to lead toxicity include substances that inhibit the ALAD enzyme and nutritional status, primarily calcium and iron intake. The interaction between these factors and ALAD may be important when considering the health effects of lead. Additionally, the genes encoding the vitamin D receptor (VDR) and the hemochromotosis-MHC Class I protein (HFE), are both polymorphic and have been recently implicated in lead poisoning susceptibility. Thus, gene-environment and gene-gene interactions may produce enhanced effects and deserve further exploration


Targets of lead toxicity

2012-02-22T14:49:02 - Aurelio Bard

Lead Poisoning

Lead is a heavy metal, naturally found in nature, often associated with Zn, Ag and S and other minerals.
For years it was used in paint industries, metal foundries, batteries for vehicles, bullets for guns.
People exposed the most to lead are metal workers, painters, families (in particular children) who live near factories that make lead dust. In these places, in fact, the soil and the groundwater are highly polluted.

People get lead poisoning from breathing its dust (from the soil, filings, paint and so on), swallowing polluted water (from leadpipes) or with the simple contact with skin and mucosa.
In the bloodstream lead spread to every organs, in particular in bones (with a half-life of about 30 years), hair follicles, hepatocytes, which contain several target enzymes. Lead in fact bonds with sulfuric group, mimicking the action of other metal cofactors, such as Fe, Ca, Zn.
Lead interacts with ALAD that takes part in the synthesis of Protoporphirine IX and acts by inhibiting Ferrochetalase that allows the bond between Fe and Protoporphirine IX. This cause a severe hypocromic anemia and the formation of ZPP.
On neurons lead interacts with NMDA receptor, blocking glutamate release.

In kidneys lead interacts with 25(OH)D-1α hydroxylase, essential for the vitamin D synthesis. A decrease of calcemia lead a loss of Calcium in skeletal muscle (that causes fatigue), cardiac failure, loss of those metabolic processes that require Calcium as second messenger.
In hepatocytes lead accumulates for the high affinity with CYP450. Because of its saturation, xenobiotic are less metabolized by the liver.
In CNS lead interacts with TPH, an enzyme that requires Fe as cofactor, involved in synthesis of the serotonin. Lead replace the iron, decreasing 5-HT levels. Severe depression can occur, more over many studies demonstrated the link between depression and immune system failure.

Often patients complain general weakness, anorexia, skeletal muscle fatigue, depression.
Haematic levels of lead are considered dangerous and harmful above 10 μg/dL in children and 25 μg/dL in adults. An easy blood test can be done to detect poisoning, as an alternative a hair follicle can be tested.
In case of acute or severe chronic poisoning a strong chelating agent is given (like an EDTA). A diet full of Fe, Ca, Zn and vitamin C is highly recommended.
To prevent lead poisoning is helpful replace old painting, leaded plumbing and clean down the house with HEPA vacuum.



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