Cholesterol lowering and bile acid excretion in the hamster with cholestyramine treatment.
Cholestyramine was administered to hamsters at 6 doses in the diet for 1 week. Plasma cholesterol, LDL + VLDL cholesterol and HDL cholesterol were measured after this period. Bile acid excretion was measured in faeces collected over the final 24 h of the experiment. A dose-response curve for each parameter measured was constructed using data from individual hamsters. For the bile acid and the cholesterol measurements a maximum response was observed at the highest doses. A correlation between the bile acids excreted over 24 h and the LDL + VLDL cholesterol showed that the maximum effect of cholestyramine on lowering plasma and lipoprotein cholesterol occurred at a submaximal excretion level of bile acids. Comparison of the efficiency of cholestyramine in reducing plasma cholesterol in the hamster with limited data in the dog and in man suggest that a greater lowering of plasma cholesterol is achieved in the dog and in man for an equivalent increase in bile acid excretion caused by the sequestrant. As is already known, cholestyramine treatment caused an increase in hepatic cholesterol 7 alpha-hydroxylase and HMG-CoA reductase activity. Interestingly in this study the novel observation was made that the bile acid sequestrant reduced the activity of hepatic acyl-CoA: cholesterol acyltransferase.
Suckling
K E
KE
Smith Kline Beecham Pharmaceuticals, Welwyn, Herts, U.K.
Benson
G M
GM
Bond
B
B
Gee
A
A
Glen
A
A
Haynes
C
C
Jackson
B
B
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D002792:Cholestyramine Resin / Q000494:pharmacology*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D002785:Sterol O-Acyltransferase / Q000378:metabolism
D001647:Bile Acids and Salts; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D002792:Cholestyramine Resin; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase; D002785:Sterol O-Acyltransferase