Lead hepatotoxicity & potential health effects.
Occupational and environmental exposures to lead (Pb), one of the toxic metal pollutants, is of global concern. Health risks are increasingly associated with environmental exposures to Pb emissions from, for example, the widespread use of leaded gasoline in developing countries. Exposure occurs mainly through the respiratory and gastrointestinal systems, and the ingested and absorbed Pb is stored primarily in soft tissues and bone. Autopsy studies of Pb-exposed patients have shown a large amount (approximately 33%) of the absorbed Pb in soft tissue stored in liver. In addition to neuronal encephalopathy observed in persons after exposure to very high concentrations of Pb, gastrointestinal colic (abdominal pain, constipation, intestinal paralysis) is a consistent early symptom of Pb poisoning in humans. Such severe gastrointestinal effects are consistently observed in patients with a blood Pb range of 30 to 80 microg/dl. Ingestion of Pb is one of the primary causes of its hepatotoxic effects. Hepatocarcinogenic effects of Pb reported in animal toxicology studies have led to new research into the biochemical and molecular aspects of Pb toxicology. Gains in the molecular understanding of Pb effects on hepatic drug metabolizing enzymes, cholesterol metabolism, oxidative stress, and hepatic hyperplasia suggest a potential role for Pb in damaging extrahepatic systems, including the cardiovascular system. This review also discusses the therapeutic potential of chelation therapy in treating Pb-induced hepatotoxicity in animals.
Mudipalli
Anuradha
A
National Center for Environmental Assessment, Office of Research & Development, U.S. EPA, North Carolina 27709, USA. Mudipalli.anu@epa.gov
D000818:Animals; D002614:Chelating Agents / Q000627:therapeutic use; D002784:Cholesterol / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004195:Disease Models, Animal; D004781:Environmental Exposure; D006418:Heme / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D007854:Lead / Q000493:pharmacokinetics / Q000633:toxicity*; D007855:Lead Poisoning / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008099:Liver / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D016273:Occupational Exposure; D018384:Oxidative Stress / Q000187:drug effects
D002614:Chelating Agents; D007854:Lead; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol