Effect of clofibrate on cholesterol metabolism in rats treated with polychlorinated biphenyls.
Serum and hepatic cholesterol content in rats treated with polychlorinated biphenyls (PCBs, KC-400) were increased compared to those of control rats. This increase of cholesterol content was reduced to control level by simultaneous administration of ethyl p-chlorophenoxyisobutyrate (CPIB). Also, when lecithin-cholesterol acyltransferase (LCAT) (EC. 2.3.1.43) activity was expressed as the net cholesterol esterification, the acyltransferase activity in rats treated with PCBs was elevated, while the elevated acyltransferase activity was brought to control level by simultaneous administration of CPIB. On the other hand, the amount of bile of rats treated with CPIB, PCBs and PCBs-CPIB was increased, but free and total cholesterol content in bile of these treated rats was decreased to 40-60% of those of control rats. Moreover, cytochrome P-450 content in liver microsomes of rats treated with CPIB, PCBs and PCBs-CPIB was increased. At the same time, cholesterol-metabolizing activity in liver microsomes of rats treated with CPIB, PCBs and PCBs-CPIB also was elevated. Similar results were obtained for drug metabolizing (aniline hydroxylation and aminopyrine N-demethylation) activity. In addition, the amount of bile acids excreted from rats treated with CPIB, PCBs and PCBs-CPIB was increased compared to that of control rats. These results suggest that hypercholesterolemia induced by oral ingestion of PCBs is recovered by CPIB treatment and that this hypocholesterolemic effect of CPIB may be related partly to the elevation of hepatic mixed function oxidase activity for cholesterol catabolism.
Nakagawa
M
M
Shimokawa
T
T
Noguchi
A
A
Ishihara
N
N
Kojima
S
S
D000818:Animals; D001646:Bile / Q000378:metabolism; D002250:Carbon Radioisotopes; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002994:Clofibrate / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D002250:Carbon Radioisotopes; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D011078:Polychlorinated Biphenyls; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D002994:Clofibrate