Cyclophosphamide and its metabolite acrolein. Some studies on their porphyrinogenic action in 17 day old chick embryo

• Published in: Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology Vol. 102; no. 1; p. 143
• Main Authors: Cochón, A C, San Martín de Viale, L C, Wainstok de Calmanovici, R
• Format: Journal Article
• Language: English
• Published: England 01-05-1992
• Subjects: 5-Aminolevulinate Synthetase - metabolism; Acrolein - pharmacology; Allylisopropylacetamide - pharmacology; Animals; Chick Embryo - drug effects; Chick Embryo - metabolism; Cyclophosphamide - metabolism; Cyclophosphamide - pharmacology; Cytochrome P-450 Enzyme System - biosynthesis; Cytochrome P-450 Enzyme System - drug effects; Cytochrome P-450 Enzyme System - metabolism; Enzyme Induction - drug effects; Gestational Age; Liver - chemistry; Liver - drug effects; Liver - enzymology; Molecular Structure; Phenobarbital - pharmacology; Porphyrins - biosynthesis; Proadifen
• ISSN: 0742-8413
• DOI: 10.1016/0742-8413(92)90056-D

1. Some studies of cyclophosphamide (CP) and its metabolite acrolein in chick embryo liver were carried out in order to investigate the mechanism of the porphyrinogenic action of CP. 2. In vitro and in vivo studies revealed that CP induced but did not activate delta-aminolaevulinic acid (ALA) synthase. 3. Pretreatments with phenobarbital (PB) or SKF-525A did not modify ALA-synthase induction produced by CP. 4. Acrolein administration neither induced ALA-synthase activity nor increased cytochrome P-450 content or led to hepatic porphyrin accumulation. 5. Time course induction of cytochrome P-450 content after administration of CP or PB was similar. 6. The results obtained would indicate that CP is a strong inducer of both ALA-synthase activity and microsomal cytochrome P-450 content in liver of 17 day-old chick embryos and that its porphyrinogenic activity is not mediated by its metabolite acrolein.