Hepatic Drug Metabolism and Haem Biosynthesis in Lead‐poisoned Rats

Abstract

1 Pretreatment of rats with intraperitoneal injections of lead was shown to result in a depression of the microsomal mixed function oxidase system, as assessed by a decrease in hepatic microsomal P-450 and b5 content and by a decrease in the activity of the enzymes aniline hydroxylase and aminopyrine demethylase. Lead had a more marked effect on cytochrome P-450 than b5. 2 The activity of the rate-limiting enzyme of haem biosynthesis, c-aminolaevulinic acid synthase, was inversely correlated with the microsomal cytochrome P-450 content. 3 The activity of the haem biosynthetic enzymes 6-aminolaevulinic acid dehydratase, coproporphyrinogen oxidase and ferrochelatase were decreased by increasing lead pretreatment. 4 The activity of the haem catabolic enzyme, haem oxygenase, was increased by lead pretreatment. IntroductionIt has long been recognized that haem synthesis in man is severely affected by increased body lead burden. This inhibition of haem production is well known to result in decreased levels of circulating haemoglobin in lead-exposed individuals. The possibility of altered drug metabolism due to inhibition of synthesis of the microsomal haemoprotein cytochrome P-450 has been the subject of a number of studies both in man and animals.Recent reports (Alvares, Kapelner, Sassa & Kappas, 1975; Meredith, Campbell, Moore & Goldberg, 1977)

Atomic Absorption Spectroscopy: Fundamentals and Applications in Medicine

“…With regard to the values of the biomarkers of Pb poisoning in blood analyzed (Tables 2, 3, 4 and 5), all of them are within the range reported by other authors (Goldberg, 1972;Tomokuni, K. & Ogata, 1976;Campbell et al, 1977;Goldberg et al 1978;Granick et al, 1978;Meredith et al 1979;Sakai et al, 1982;Barbosa et al, 2005). Although the standard deviation values can be considered high for some parameters, this should not be attributed to the methodology used given the biological variability that is observed in the study population.…”

“…The above table shows that in both, severe and slight Pb poisoning, the increases in the concentration of blood Pb are associated with significant inhibition of ALA-D activity (Campbell et al, 1977;Goldberg et al, 1978;Sakai et al, 1982) and with significant increases of protoporphyrin IX concentrations (Goldberg et al, 1978;Meredith et al, 1979). After treatment the values still remain significantly altered, indicating that the patients need a new series of treatment, because of the guidelines therapy is performed during five days with breaks in which they carry out checks on biomarkers.…”

Characterizing Golden Eagle Risk to Lead and Anticoagulant Rodenticide Exposure: A Review

“…An inverse dose-effect relationship between lead exposure and P-450 content of hepatic microsomes and also activity of microsomal mixed-function oxygenases has been observed (Goldberg et al 1978). Increasing duration of exposure to lead was associated with decreasing microsomal P-450 content and decreasing microsomal heme content ).…”

Lead and its Effects on Cytochromes P450

“…The potential for a detrimental interaction between lead and the cytochromes P450 is reflected by the previous work in animal studies [8][9][10]. Goldberg et al [8] injected mice intraperitoneally with lead acetate over a period of 14 days.…”

“…The potential for lead to modulate the activity of cytochromes P450 is reflected by previous animal studies [8][9][10]. While data in animals suggest a decrease in CYP function with lead exposure, there are little data in humans.…”