RT Journal Article
SR Electronic
T1 Metabolism of styrene oxide in different human fetal tissues.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 302
OP 305
VO 10
IS 4
A1 G M Pacifici
A1 A Rane
YR 1982
UL http://dmd.aspetjournals.org/content/10/4/302.abstract
AB Epoxide hydrolase and glutathionetransferase activities toward [7-3H]styrene 7,8-oxide were measured in the microsomal and cytosolic fractions, respectively, of human fetal liver, lungs, kidneys, adrenal glands, gut, and placenta. Both activities were present at significant rates in all the tissue specimens studied. Epoxide hydrolase activities in the liver (5.98 +/- 0.62 nmol/min/mg) and the adrenal glands (3.57 +/- 0.46 nmol/min/mg) were considerably higher than the corresponding activities in the lungs, kidneys, gut, and placenta, in which organs the mean values ranged from 0.27 to 0.55 nmol/min/mg. The glutathionetransferase activity was more uniformly distributed among the various tissues. It ranged between 5.56 +/- 0.46 and 4.21 +/- 0.39 nmol/min/mg in the liver, the adrenals, the kidneys, the lungs and the placenta. The gut had, however, significantly lower activity than the other tissues (2.56 +/- 0.24 nmol/min/mg). Our data demonstrate differences in the ontogenic development of the styrene oxide metabolism between man and animals and thus, they point out the lack of relevance of fetal animal studies for prediction of human fetal metabolism. The hepatic and extra-hepatic capacity of the human fetus to detoxify epoxides may be biologically important in view of the fact that xenobiotics traversing the placenta to a great extent reach the fetal organs directly (through the venous duct) without preceding passage through the liver.