[Retracted] Biomedical Implications of Heavy Metals Induced Imbalances in Redox Systems
Table 2
The physical, chemical, and clinical properties of heavy metals included in the review.
Physical/chemical/clinical properties
Heavy metals
Arsenic (As)
Lead (Pb)
Cadmium (Cd)
Mercury (Hg)
Absorption
GI inorganic: trivalent and pentavalent salts >90%; organic: also bound as tri- and pentavalent >90%; inhalation: uptake is dependent upon particle size
Skin: alkyl lead compounds, because of lipid solubility (methyl and tetraethyl lead); inhalation: up to 90% depending upon particle size; GI: adults 5 to 10%, children 40%
Inhalation 10 to 40%; GI 1.5 to 5%
GI: inorganic salts may be absorbed and may be converted to organic mercury in the gut by bacteria; inhalation: elemental Hg completely absorbed
Distribution
Accumulates in lung, heart, kidney, liver, muscle, and neural tissue; concentrates in skin, nails, and hair
Initially carried in red cells and distributed to soft tissues (kidney and liver); bone, teeth, and hair mostly as a phosphate salt
Initially bound to albumin and blood cells, subsequently to metallothionene in liver and kidney
Elemental Hg (vapor) crosses membranes well and rapidly moves from lung to CNS. Organic salts (lipid soluble) are evenly distributed, intestinal (intracellular)-fecal elimination. Inorganic salts concentrate in blood, plasma, and kidney (renal elimination)
Half-life
7 to 10 h
Blood: 30–60 days; bone: 20–30 years
10 to 20 years
60 to 70 days
Sources of exposure
GI: well water, food. Environmental: by-product of smelting ore, as Ga in semiconductors, herbicides, and pesticides; inhalation: fumes and dust from smelting
GI: paint, pottery, moonshine; inhalation: metal fumes skin: tetraethyl lead in gasoline
Environmental: electronics and plastic industry; seed fungicide treatment; dentistry
Mechanism of toxicity
Membranes: protein damage of capillary endothelium increased vascular permeability leading to vasodilation and vascular collapse; inhibition of sulfhydryl group containing enzymes; inhibition of anaerobic and oxidative phosphorylation (substitutes for inorganic phosphate in synthesis of high-energy phosphates)
Inhibition of heme biosynthesis; heme is the essential structural component of hemoglobin, myoglobin, and cytochromes. Binds to sulfhydryl groups (-SH groups) of proteins
Inhalation: lung, local irritation, and inhibition of alpha1-antitrypsin associated with emphysema; oral: kidney: proximal tubular injury, (proteinuria) associated with beta2-acroglobulin
Dissociation of salts precipitates proteins and destroys mucosal membranes; necrosis of proximal tubular epithelium; inhibition of sulfhydryl (-SH) group containing enzymes
Diagnosis
History of exposure; blood and urinary levels (acute); hair or fingernail (chronic)
History of exposure, whole blood level (children >25 ug/dL and adults >50 ug/dL), protoporphyrin levels in RBCs >40 ug/dL, urinary lead >80 μg/dL
History of exposure, whole blood Cd level >80 μg/dL
History of exposure; blood mercury
Symptoms
Acute-damage to mucosa, sloughing, hypovolemic shock, fever, GI discomfort/pain, anorexia; chronic weakness, GI, hepatomegaly (jaundice > cirrhosis), melanosis, arrhythmias, peripheral neuropathy, peripheral vascular disease (blackfoot disease); carcinogenicity: epidemiologic evidence; liver angiosarcoma and skin and lung cancer
Acute: nausea, vomiting, thirst, diarrhea/constipation, abdominal pain, hemoglobinuria, and oliguria leading to hypovolemic shock Chronic: GI: lead colic (nausea, vomiting, abdominal pain) NMJ: lead palsy (fatigue, wrist drop) CNS: lead encephalopathy (headache, vertigo, irritation, insomnia, CNS edema)
Removal from exposure Acute: supportive therapy: fluid, electrolyte replacement, blood pressure support (dopamine); chronic: penicillamine w/o dialysis arsine gas (AsH3) acts as a hemolytic agent with secondary to renal failure. Supportive therapy: transfusion; chelators have not been shown to be beneficial
Removal from exposure, treatment with chelators like CaNa2EDTA, BAL, dimercaprol, D-penicillamine
Removal from exposure, chelation therapy with CaNa2EDTA, BAL but BAL-Cd complex is extremely toxic, so it is not used
Removal from exposure; Hg and Hg salts >4 μg/dL: 2,3-dimercaptopropanol (BAL), β, β-dimethyl cysteine (penicillamine), most effective is N-acetyl-β, β-dimethyl cysteine (N-acetyl-penicillamine); methyl Hg-supportive treatment (nonabsorbable thiol resins can be given orally to reduce methyl Hg level in gut)