Differential induction of cytochrome P-450 by the enantiomers of trans-stilbene oxide.
Optically pure (+)- and (-)-trans-stilbene oxide (TSO) enantiomers were administered to immature male Sprague-Dawley rats. (+)-TSO was the more potent inducer of liver microsomal cytochrome P-450-dependent monooxygenases. The greater potency of (+)-TSO may be explained on the basis of stereoselective metabolism since a far greater concentration of TSO was found in liver microsomes of (+)-TSO-treated rats. Furthermore, of the enzymes known to metabolize TSO, cytosolic epoxide hydrolase turned over the (-)-TSO enantiomer at a faster rate, consistent with the greater persistence of the (+)-enantiomer. Although this report is of chiral effects in potency of enzyme induction, stereoselective metabolism (i.e. disposition) rather than inherent structural characteristics (recognition) may be responsible for these effects.
Rauch
P
P
Institute of Toxicology, University of Mainz, Federal Republic of Germany.
Püttmann
M
M
Oesch
F
F
Okamoto
Y
Y
Robertson
L W
LW
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003600:Cytosol / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000502:physiology; D013237:Stereoisomerism; D013267:Stilbenes / Q000378:metabolism / Q000494:pharmacology*
D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D013267:Stilbenes; D003577:Cytochrome P-450 Enzyme System; C025906:stilbene oxide