Malotilate, a hepatoprotectant, suppresses CYP2E1 expression in rats.
The expression of CYP2E1 was examined in hepatic tissue from rats treated with malotilate (MT), a hepatoprotectant. Microsomal p-nitrophenol hydroxylase activity in MT-treated rats was decreased to 66% and 47% of control activity at day 2 and 3 post-treatment. SDS-PAGE and immunoblot analyses of hepatic microsomes prepared from MT-treated rats showed that CYP2E1 levels were decreased below the limit of detectability. In contrast, CYP2B1 levels were increased in MT-treated microsomes, as assessed by immunoblot analyses. MT, however, failed to modulate CYP1A expression. RNA hybridization analysis revealed that CYP2E1 mRNA levels failed to change significantly by day 2 or 3 post-treatment, whereas microsomal epoxide hydrolase mRNA levels were elevated approximately 3-fold at the same time points. These results demonstrate that MT effectively suppresses CYP2E1 expression in the absence of transcriptional inactivation.
Kim
S G
SG
College of Pharmacy, Duksung Women's University, Seoul, Korea.
Kwak
J Y
JY
Lee
J W
JW
Novak
R F
RF
Park
S S
SS
Kim
N D
ND
D000818:Animals; D001483:Base Sequence; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008297:Male; D008314:Malonates / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D017931:DNA Primers; D008314:Malonates; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate