Liver damage induced by bile duct ligation affects CYP isoenzymes differently in rats.
We examined the influence of liver damage induced by bile duct ligation on the activity and the expression of hepatic cytochrome P450 (CYP) 1A, 2B, 2C6, 2C11, 2E1 and 3A2 in male Sprague-Dawley rats. In the ligation group, testosterone 2 alpha-, 16 alpha-, and 6 beta-hydroxylase activities were severely decreased, whereas ethoxyresorufin O-deethylase and progesterone 21-hydroxylase activities relatively remained. Pentoxyresorufin O-deethylase and chlorzoxazone 6-hydroxylase activities were reduced to approximately one thirds those of control. The protein contents of these isoenzymes expressed in hepatic microsomes of the ligation group were decreased to 45%, 32%, 79%, 13%, 58%, and 23% of control for CYP1A, 2B, 2C6, 2C11, 2E1 and 3A2, respectively. The rank order of magnitude of the influence of bile duct ligation on CYP isoenzymes, assessed by the reduction in the enzyme activity and the protein content, corresponded with each other except CYP1A. The reduction of the enzyme activities significantly correlated with the reduction in the protein contents of different isoenzymes. These results suggested that bile duct ligation affected CYP isoenzyme activities and contents with different extent.
Tateishi
T
T
Department of Pharmacology, St. Marianna University School of Medicine, Kanagawa, Japan.
Watanabe
M
M
Nakura
H
H
Tanaka
M
M
Kumai
T
T
Kobayashi
S
S
D000818:Animals; D001652:Bile Ducts / Q000601:surgery; D002780:Cholestasis, Intrahepatic / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008026:Ligation; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System