Mechanisms of lead-induced poisoning.
Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic circulatory, neurological, hematological, gastrointestinal, reproductive and immunological pathologies. The mechanism of lead induced toxicity is not fully understood. The prime targets to lead toxicity are the heme synthesis enzymes, thiol-containing antioxidants and enzymes (superoxide dismutase, catalase, glutathione peroxidase, glucose 6-phosphate dehydrogenase and antioxidant molecules like GSH). The low blood lead levels are sufficient to inhibit the activity of these enzymes and induce generation of reactive oxygen species and intensification oxidative stress. Oxidative stress plays important role in pathogenesis of lead-induced toxicity and pathogenesis of coupled disease. The primary target of lead toxicity is the central nervous system. There are different cellular, intracellular and molecular mechanisms of lead neurotoxicity: such as induction of oxidative stress, intensification of apoptosis of neurocites, interfering with Ca(2+) dependent enzyme like nitric oxide synthase. Population studies have demonstrated a link between lead exposure and subsequent development of hypertension and cardiovascular disease. The vascular endothelium is now regarded as the main target organ for the toxic effect of lead. Lead affects the vasoactive function of endothelium through the increased production of reactive oxygen species, inactivation of endogenous nitric oxide and downregulation of soluble guanylate cyclase by reactive oxygen species, leading to a limiting nitric oxide availability, impairing nitric oxide signaling. This review summarizes recent findings of the mechanism of the lead-induced toxicity and possibilities of its prevention.
Nemsadze
K
K
Tbilisi State Medical University.
Sanikidze
T
T
Ratiani
L
L
Gabunia
L
L
Sharashenidze
T
T
D004730:Endothelium, Vascular / Q000187:drug effects; D004781:Environmental Exposure; D006801:Humans; D007854:Lead / Q000633:toxicity*; D007855:Lead Poisoning / Q000097:blood / Q000201:enzymology* / Q000517:prevention & control; D009784:Occupational Diseases / Q000097:blood / Q000201:enzymology* / Q000517:prevention & control; D018384:Oxidative Stress
D007854:Lead