Nowadays, exposure to lead is a global health problem. Lead is one of the most
important toxic elements, it affects impact on human health through the food chain.
Lead applications are various, this element has a special role in industries, including smelting, battery manufacturing, and mining, as a result of industrialization discharging industrial units that located in close proximity to rivers lead to polluting water bodies. Also, this element uses as a fertilizer and pesticide in agriculture, so it pollutes soils and environment. vehicular traffic systems are the most important problem in urban, that lead has an important role in it.
The lead entrance into bloodstream is gastrointestinal, respiratory tracts and also skin and mucosa but not as much as others ways, the main absorption route is respiratory tract (30-70%). Gastrointestinal absorption in children increases up to 50%, but in adults is normally less(10%). Exposure to lead by inhalation in adults is 4 times higher than children. iron deficiency, low dietary calcium and fasting promote lead absorption. organic lead especially tetraethyl lead gets absorbed through the dermal and mucosal route.
After absorption lead gets bound to various soft and hard tissues, such as hair dense, bone, teeth (hard tissue) and brain, spleen, kidney, bone marrow, lungs (soft tissue) and the rest is excreted with urine, feces, and sweating )7). Most of the circulating lead is bound to red blood cells for about 30-35 days then it spreads into the soft tissues over the 4-6 weeks and approximately 1% of the absorbed lead is found in serum and plasma. lead is stored in the bones (95%), these are the primary lead pool. As a result of long lead half-life, patients suffer lead toxicity even after the cessation of any external source of lead toxicity (9).
The hypothalamus pituitary thyroid (HPT) axis controls thyroid function through thyrotropin releasing hormone (TRH), thyroid stimulating hormone (TSH), and the Thyroid hormones such as thyroxine (T4) and triiodothyronine (T3). Most of the time T4 and T3 are bound to thyroxine-binding globulin, transthyretin, and albumin, less than 1% circulation T4 and T3 are unbound and active. In peripheral tissues, type 1 and type 2 deiodinases convert T4 to T3; T3 in turn binds thyroid receptors ? and ? and initiates target gene expression (10). Disruption of TH synthesis, transport, deiodination, and metabolism can result in clinical or subclinical thyroid diseases (10). Environmental chemicals same as lead might change TH levels via several mechanisms, including TH-binding proteins, disruption of iodine transport, thyroid peroxidase, deiodinases, and receptor binding (11).
Lead is an environmental chemical that affect on the hypothalamic-pituitary axis causing blunted TSH, FSH/LH, and GH responses to TRH, GNRH, and GHRH stimulation. It can also affect Thyroid hormone kinetics.
Thyroid hormones activity destroyed by thyroid axis`s defection and T4 metabolism`s alteration and protein’s binding.
Lead is a bivalent cation, it interferences the ALAD enzyme activity, ALAD catalyzes the condensation of 2 molecules of delta-aminolevulinate to form porphobilinogen, decreasing heme body pool as a result of ALAD`s inhibition, blood lead level over than 20 ?g/dl inhibits 50% ALAD`s activity. Delta-ALAD`s inhibition leads decreasing heme synthesis and GABA( gamma-Aminobutyric acid )releasing in the CNS (central nervous system) and increasing urinary aminolevulinic acid (ALA),but it can be recognized when blood lead levels over 35 ?g/dL in adults.
previous studies on various populations show, there are strong relationships between the ALAD2 allele and increased blood and bone lead levels (16) also lead can affect glucose-6-phosphate dehydrogenase that lead to anemia.
Ferrochelatase catalyzes terminal step in the biosynthesis of heme, converting protoporphyrin IX into heme, also it catalyzes the insertion of iron into protoporphyrin IX. Ferrochelatase`s activity impaired by lead (18).
Also lead can affect the activity of pyrimidine 5′-nucleotidase, enzyme activity is inhibited by lead which leads to decreased red blood cell counts and eventually anemia.
observation of basophilic stippling and premature erythrocyte hemolysis in the blood smear are the hematologic signs of lead poisoning
Blood hemoglobin levels do not change as a result of lead exposure until blood lead levels are 50 ?g/dl for adults (18).
Lead toxicity changes calcitropic hormones’ homeostasis and it increases skeletal disorders`s risk (12).
Now, it’s well accepted that lead (Pb) has many toxic influences on the health of humans, several studies have been conducted on occupational exposure and biologic evaluation of lead in Iranian workers, but few studies have been carried out on the effects of lead on thyroid parameters and blood parameters.