LIVER-DAMAGE INDUCED BY BILE-DUCT LIGATION AFFECTS CYP ISOENZYMES DIFFERENTLY IN RATS

We examined the influence of liver damage induced by bile duct ligatio n 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 lig ation group, testosterone 2 alpha-, 16 alpha-, and 6 beta-hydroxylase activities were severely decreased, whereas ethoxyresorufin O-deethyla se and progesterone 21-hydroxylase activities relatively remained. Pen toxyresorufin 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 l igation group were decreased to 45%, 32%, 79%, 13%, 58%, and 23% of co ntrol for CYP1A, 2B, 2C6, 2C11, 2E1 and 3A2, respectively. The rank or der of magnitude of the influence of bile duct ligation on CYP isoenzy mes, assessed by the reduction in the enzyme activity and the protein content, corresponded with each other except CYP1A. The reduction of t he enzyme activities significantly correlated with the reduction in th e protein contents of different isoenzymes. These results suggested th at bile duct ligation affected CYP isoenzyme activities and contents w ith different extent.