Acute Effect of Amitriptyline, Phenobarbital or Cobaltous Chloride on δ-Aminolevulinic Acid Synthetase, Heme Oxygenase and Microsomal Heme Content and Drug Metabolism in Rat Liver

Abstract

Cobaltous chloride (CoCl₂) caused very marked decreases of cytochrome P-450, b₅ and total heme contents and an increase of heme oxygenase activity. On the contrary, phenobarbital (PB) increased hepatic drug-metabolizing enzymes, but the total heme content remained unchanged. On the other hand, amitriptyline (AMT) caused a marked increase of δ-aminolevulinic acid (δ-ALA) synthetase activity at 12 and 24 hr. In addition, the contents of total heme and cytochrome b₅ and the activities of aminopyrine (AM) N-demethylase and aniline (AN) hydroxylase at 24 hr were also increased by AMT, whereas cytochrome P-450 content did not change. This may be explained by the fact that AMT would increase hepatic heme synthesis through the prolonged induction of δ-ALA synthetase, but it may not cause an increase in cytochrome P-450 heme because there are increases in the contents of cytochrome b₅ and total heme.