Induction of hepatic drug-metabolizing enzymes by chlornitrofen (CNP) and CNP-amino in rats and mice.
The induction of hepatic drug-metabolizing enzymes by chlornitrofen (CNP) and CNP-amino was studied in the liver of male rats and mice. CNP-amino increased the activities of 7-pentoxyresorufin O-depentylase (PROD) and 7-benzyloxyresorufin O-debenzylase (BROD) as CYP2B1-dependent monooxygenase 3.6- and 4.1-fold in rats. On the contrary, these enzyme activities in mice were induced by CNP rather than by CNP-amino. Furthermore, immunoblotting showed that the protein levels of CYP2B subfamily cytochrome P450 (P450) in liver microsomes of rats and mice were increased by CNP or CNP-amino. Phase II drug-metabolizing enzymes, UDP-glucuronyltransferase (UGT) and glutathione S-transferase (GST) levels in mice were also significantly increased from 1.4 to 2.5-fold by CNP or CNP-amino. However, neither CNP nor CNP-amino affected UGT and GST in rats. These results suggest that CNP and or CNP-amino induce the P450 isoforms of CYP2B subfamily in the rat and mouse liver, and that the inducibility of drug-metabolizing enzyme by the compounds is different between rats and mice.
Hanioka
N
N
Division of Environmental Chemistry, National Institute of Health Sciences, Tokyo, Japan.
Nakano
K
K
Jinno
H
H
Hamamura
M
M
Takahashi
A
A
Yoda
R
R
Nishimura
T
T
Ando
M
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D015151:Immunoblotting; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009153:Mutagens / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D010647:Phenyl Ethers / Q000633:toxicity*; D051381:Rats; D013329:Structure-Activity Relationship; D014874:Water Pollutants, Chemical / Q000633:toxicity
D006540:Herbicides; D009153:Mutagens; D010647:Phenyl Ethers; D014874:Water Pollutants, Chemical; C010422:2,4,6-trichlorophenyl 4-nitrophenyl ether; C067259:2,4,6-trichlorophenyl-4'-aminophenyl ether; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase