Cytochrome P450 isozyme induction by methyl ethyl ketone and m-xylene in rat liver.
The rat hepatic cytochrome P450 induction pattern caused by administration of a high peroral dose of methyl ethyl ketone (MEK, 1.4 ml/kg once daily for 3 consecutive days) and m-xylene (1.0 ml/kg X 3) was studied by catalytic activity and immunoblotting techniques. MEK caused a marked increase in the amount of P450 isozymes belonging to the phenobarbital- and ethanol-inducible P450 subfamilies P450IIB and P450IIE, respectively. Catalytic activities linked with these isozymes, pentoxyresorufin O-depentylase (P450IIB), aniline hydroxylase, and N-nitrosodimethylamine N-demethylase (P450IIE), were also increased (18.0-, 5.4-, and 2.4-fold, respectively). The activity of ethoxyresorufin O-deethylase, which is predominantly linked with the polycyclic aromatic hydrocarbon-inducible P450 isozymes, was also increased 2.3-fold without an apparent increase in the amount of the respective P450 protein (P450IA). m-Xylene caused a similar induction pattern with less effect on P450IIE. Simultaneous administration of MEK and m-xylene resulted in an additive or, in the case of pentoxyresorufin O-depentylase, a potentiating effect on P450-linked catalytic activities. These data indicate that MEK and m-xylene elicit a qualitatively similar induction of P450 isozymes, which may play a role in the metabolic interactions of these compounds.
Raunio
H
H
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Liira
J
J
Elovaara
E
E
Riihimäki
V
V
Pelkonen
O
O
D000818:Animals; D002074:Butanones / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014992:Xylenes / Q000378:metabolism / Q000494:pharmacology*
D002074:Butanones; D007527:Isoenzymes; D014992:Xylenes; D000431:Ethanol; C005222:methylethyl ketone; D003577:Cytochrome P-450 Enzyme System; C031285:3-xylene