Hepatic microsomal drug metabolism in the pregnant rat
| Autor: | R. G. Turcan, A. M. Symons, Dennis V. Parke |
|---|---|
| Rok vydání: | 1982 |
| Předmět: |
Cytochrome
Health Toxicology and Mutagenesis Aniline Hydroxylase Pharmacology Toxicology Biochemistry Substrate Specificity chemistry.chemical_compound Cytochrome P-450 Enzyme System Pregnancy Phosphatidylcholine medicine Animals Phospholipids Phosphatidylethanolamine biology Ethylmorphine-N-Demethylase Rats Inbred Strains General Medicine Ethylmorphine Enzyme assay Rats Pharmaceutical Preparations chemistry Microsomes Liver biology.protein Microsome Pregnancy Animal Gestation Female Oxidoreductases Drug metabolism Protein Binding medicine.drug |
| Zdroj: | Xenobiotica. 12:365-374 |
| ISSN: | 1366-5928 0049-8254 |
| DOI: | 10.3109/00498258209052477 |
| Popis: | 1. Hepatic microsomal drug metabolism determined with the substrates aniline (p-hydroxylation), ethylmorphine (N-demethylation) and p-nitrobenzoic acid (reduction), decreased during gestation in the rat to 53-73% of non-pregnant control levels by day 20 of gestation. 2. Enzyme activity remained low at one day post-partum, but had returned to control non-pregnant levels by five days post-partum. 3. The total capacity of the liver to metabolize drugs remained unchanged or increased because liver weight was increased by up to 40% during pregnancy. 4. Changes in drug metabolism were not related to alterations in the concentration, substrate-induced binding affinity (Ks) or maximal spectral change (delta Amax) of cytochrome P-450. 5. Alterations in hepatic drug metabolism are possibly mediated via changes in microsomal phospholipids and/or the cytochrome P-450 spin-state equilibrium as as pregnancy was associated with a decrease in (a) microsomal total phospholipids, (b) the phosphatidylcholine to phosphatidylethanolamine ratio and (c) the high-spin form of ferricytochrome P-450. |
| Databáze: | OpenAIRE |
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