Lead intoxication: Effects on cytochrome P-450-mediated hepatic oxidations

Alvito P. Alvares, Alf Fischbein, Shigeru Sassa, Karl E. Anderson, Attallah Kappas

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

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 δ-aminolevulinic acid dehydratase, increased erythrocyte protoporphyrin levels, and increased urinary excretion of δ-aminolevulinic acid. Chelation therapy greatly alleviated the inhibitory effects on dehydratase activity and decreased urinary δ-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.

Original languageEnglish (US)
Pages (from-to)183-190
Number of pages8
JournalClinical Pharmacology and Therapeutics
Volume19
Issue number2
DOIs
StatePublished - Feb 1976
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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