摘要:

The metabolism of (24-14C]lithocholic acid was studied in the microsomal fraction of fetal human liver homogenates. Fetal livers were obtained at legal abortions performed between wk 14 and 24. Product formation was analyzed by thin-layer chromatography, liquid chromatography, and gas chromatography-mass spectrometry. From wk 14 lithocholic acid was hydroxylated in several positions. Hyodeoxycholic acid (3α,6α-dihydroxy-5β-cholanoic) and lβ,3α-dihydroxy-5β-cholanoic acid were identified among the products. The 3β-isomer of the former acid, 6αhydroxy- 3-oxo-5β-cholanoic acid and a 2-hydroxylithocholic acid were tentatively identified. Two other metabolites carried a hydroxyl group in an unknown position, one of them probably at an angular methyl group. The highest total conversions per mg of microsomal protein were obtained with preparations from 18 wk fetuses. The results are discussed with particular reference to the role of lithocholic acid in fetal hepatotoxicity. (Pediatr Res 21: 99- 103,1987)

ISSN:0031-3998    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Tetrahydrocannabinol (THC), the active component in marijuana smoke, crosses the placenta and is a potential fetotoxic agent. In both human and animal studies, the most consistent fetal effect of THC is intrauterine growth retardation. Since fetal somatic growth is dependent on placental transfer of nutrients, including essential amino acids, we studied the effect of THC upon the in vitro uptake of amino acid by term human placental slices. Uptake of α-amino isobutyric acid was inhibited in a dose-dependent fashion, correlating with the log of the dose (1-100 µM THC;r=0.945;p<0.01). Compared to control tissue, significant impairment of a-amino isobutyric acid uptake began at 20 tiM THC. Similar results were found for valine. The time course (30-120 min) for a-amino isobutyric acid uptake showed linearity for both control and THC- (50 µM) treated tissue, but there was a marked reduction in the THC slope. Uptake of a-amino isobutyric acid was significantly reduced at all times. The sustained effect of THC was slightly, but significantly, reversed by removal of THC from the medium after 90 min of 50 nM THC exposure. Only partial reversal may have been due to the 15- to 20-fold accumulation of THC in the placental tissue. Uptake kinetics showed noncompetitive inhibition with decreased Vmax: control Vmax=51.66 ± 6.26 versus 50 µM THC=26.96 ± 6.22 (mmol/ liter intracellular water per h) (p<0.01); and no change in diffusion constant (Km): control Km=0.78 ± 0.08 versus 50 µM THC=0.80 ± 0.09 (mM). In addition, 50 µM THC caused a modest increase in Kd, but the difference was not significant: control Kd=3.82 ± 0.29 versus 50 µM THC=5.19 ± 1.03 (h-1). Using actively transported amino acids as an index, the results of these experiments suggest that THC may be placento-toxic. (Pediatr Res 21:104-107,1987

ISSN:0031-3998    

出版商:OVID    

年代:1987

数据来源: OVID