Lead intoxication

Effects on cytochrome P-450-mediated hepatic oxidations

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

Research output: Contribution to journalArticle

49 Citations (Scopus)

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
StatePublished - Feb 1976
Externally publishedYes

Fingerprint

Chelation Therapy
Cytochrome P-450 Enzyme System
Antipyrine
Aminolevulinic Acid
Liver
Ethylmorphine-N-Demethylase
Erythrocytes
Aniline Hydroxylase
Porphobilinogen Synthase
Hydro-Lyases
Hexobarbital
Steel
Biosynthetic Pathways
Enzymes
Heme
Pharmaceutical Preparations
Lead

ASJC Scopus subject areas

  • Pharmacology

Cite this

Lead intoxication : Effects on cytochrome P-450-mediated hepatic oxidations. / Alvares, Alvito P.; Fischbein, Alf; Sassa, Shigeru; Anderson, Karl; Kappas, Attallah.

In: Clinical Pharmacology and Therapeutics, Vol. 19, No. 2, 02.1976, p. 183-190.

Research output: Contribution to journalArticle

Alvares, AP, Fischbein, A, Sassa, S, Anderson, K & Kappas, A 1976, 'Lead intoxication: Effects on cytochrome P-450-mediated hepatic oxidations', Clinical Pharmacology and Therapeutics, vol. 19, no. 2, pp. 183-190.
Alvares, Alvito P. ; Fischbein, Alf ; Sassa, Shigeru ; Anderson, Karl ; Kappas, Attallah. / Lead intoxication : Effects on cytochrome P-450-mediated hepatic oxidations. In: Clinical Pharmacology and Therapeutics. 1976 ; Vol. 19, No. 2. pp. 183-190.
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