| Autor: |
Rifkind, Arleen, Lauersen, Niels, Bennett, Soja, New, Maria |
| Zdroj: |
Pediatric Research; April 1974, Vol. 8 Issue: 4 p366-366, 1p |
| Abstrakt: |
Knowledge of fetal drug metabolism is a necessary prerequisite for determining the safe and rational use of drug therapy during pregnancy. Heme synthesis and drug metabolism were studied in 40 human fetuses aborted by hysterotomy and prostaglandins. Δ aminolevulinic acid synthetase (ALAS), the rate limiting enzyme in heme synthesis, could be measured in livers and adrenals of fetuses aborted by hysterotomy but not in fetuses aborted by prostaglandins. Mean levels of ALAS ± SE were 74.3 ± 6.4 mμmol/gm liver in 5 fetuses aborted by hysterotomy. Aryl hydrocarbon hydroxylase activity (AHH) was highest in the adrenal gland and progressively lower in liver, intestine, testes, kidney and lung in fetuses from both groups. AHH activity in the adrenal gland was positively correlated with the concentration of microsomal cytochrome P-448 and negatively correlated with the concentration of cytochrome P-420. Secobarbital when added to human fetal liver and adrenal microsomes resulted in a type II difference spectrum (peak 430 nm, trough 406 nm) although when added to microsomes from chick embryos a type I spectrum (peak 385 nm, trough 419 nm) resulted. These studies 1) supply the first reported measurements of ALAS in human fetal tissues, 2) show that fetuses aborted by prosta-glandins are useful for studies of AHH activity, 3) provide evidence that AHH in the fetal adrenal is mediated by cytochrome P-448 and 4) show species differences in substrate binding to embryonic microsomal proteins. |
| Databáze: |
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