Effect of biliary obstruction and internal biliary drainage on hepatic cytochrome P450 isozymes in rats.
OBJECTIVE
To investigate the total cytochrome P450 (CYP) content, microsomal mixed-function oxidase (MFO) activity, and expression of mRNAs for various CYP isozymes in a simple rat model of reversible obstructive jaundice.


METHODS
Obstructive jaundice was created in male rats by causing bile duct obstruction with polyester tape. In another group of rats, bile duct obstruction was followed by internal biliary drainage after releasing the tape. The expression of various CYP isozyme mRNAs was semi-quantitatively assessed by competitive RT-PCR.


RESULTS
The total CYP content and microsomal MFO activity showed a significant decrease after biliary obstruction, but returned to respective control levels after biliary drainage. A marked reduction in the expression of CYP1A2, 2B1/2, 2C11, 2E1, 3A1, and 3A2 mRNA was detected during biliary obstruction, while expression increased significantly toward the control level after biliary drainage. Although expression of CYP4A1 mRNA showed no reduction during biliary obstruction, it still increased significantly after biliary drainage.


CONCLUSIONS
These results suggest that not only obstructive jaundice, but also the subsequent internal biliary drainage may affect regulatory medications of the synthesis of individual CYP isozymes differently.
Fukushima
Shintaro
S
Third Department of Internal Medicine, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan. fukushis@takii.kmu.ac.jp
Okuno
Hiroyasu
H
Shibatani
Nobuyuki
N
Nakahashi
Yoshitsugu
Y
Seki
Toshihito
T
Okazaki
Kazuichi
K
D000818:Animals; D002779:Cholestasis / Q000201:enzymology* / Q000628:therapy*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013396:Suction / Q000379:methods*
D007527:Isoenzymes; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases