Lead intoxication: effects on cytochrome P-450-mediated hepatic oxidations.
Acute administration of lead to rats caused significant decreases in cytochrome P=450, ethylmorphine N-demethylase, and aniline hydroxylase activities and prolonged hexobarbital-induced sleeping times. However, chronic administration of lead to weanling rats caused no significant changes in hepatic cytochrome P-450 levels or in the microsomal oxidative enzymes over a 12-wk period. Eight patients exposed to lead in the process of burning through lead-painted steel structures for at least 3 mo showed marked effects of chronic lead intoxication on the erythropoietic system: inhibition of erythrocyte delta-aminolevulinic acid dehydratase, increased erythrocyte protoporphyrin levels, and increased urinary excretion of delta-aminolevulinic acid. Chelation therapy greatly alleviated the inhibitory effects on dehydratase activity and decreased urinary delta-aminolevulinic acid excretion. The plasma elimination rate of antipyrine, a drug primarily metabolized by hepatic microsomal enzymes, was determined in the 8 subjects prior to and following chelation therapy. In 7 of 8 subjects, chelation therapy shortened the antipyrine half-lives, but the effect was minimal. These studies show that chronic lead exposure results in significant hematopoietic inhibition of the heme biosynthetic pathway without causing significant changes in hepatic cytochrome P-450-associated enzymic activities.
D000328:Adult; D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D006207:Half-Life; D006591:Hexobarbital / Q000494:pharmacology; D006801:Humans; D007854:Lead / Q000097:blood / Q000494:pharmacology; D007855:Lead Poisoning / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D008875:Middle Aged; D009784:Occupational Diseases / Q000201:enzymology; D010084:Oxidation-Reduction; D051381:Rats; D012890:Sleep / Q000187:drug effects
D007854:Lead; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D000815:Aniline Hydroxylase; D005037:Ethylmorphine-N-Demethylase; D000983:Antipyrine