HEPATIC DRUG METABOLISM AND HAEM BIOSYNTHESIS IN LEAD‐POISONED RATS

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Abstract
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. The activity of the rate‐limiting enzyme of haem biosynthesis, δ‐aminolaevulinic acid synthase, was inversely correlated with the microsomal cytochrome P‐450 content. The activity of the haem biosynthetic enzymes δ‐aminolaevulinic acid dehydratase, coproporphyrinogen oxidase and ferrochelatase were decreased by increasing lead pretreatment. The activity of the haem catabolic enzyme, haem oxygenase, was increased by lead pretreatment.