The purpose of this study was to compare the efficacy of
GT16-239, an alkylated, cross-linked poly(
allylamine)
bile acid sequestrant with
cholestyramine on
cholesterol and
bile acid metabolism, and early aortic
atherosclerosis in hypercholesterolemic male F1B Golden Syrian hamsters. In this controlled study, 42 hamsters were divided into six groups and were fed a chow-based hypercholesterolemic diet supplemented with
a 10% oil blend (55% coconut/45% corn), 0.1%
cholesterol (w/w) (control) and either 0.9 or 1.2%
cholestyramine or 0.2, 0.4 or 0.6%
GT16-239 for 13 weeks. Laboratory analyses included evaluating plasma
lipoprotein cholesterol and
triglyceride concentrations, hepatic
HMG-CoA reductase and
7 alpha-hydroxylase activities, fecal excretion of
bile acids and neutral
sterols, hepatic
cholesterol concentrations, and early
atherosclerosis (aortic fatty streak area). Relative to the control diet, the 0.6%
GT16-239 versus the 1.2%
cholestyramine significantly inhibited the elevation of plasma
lipoprotein total
cholesterol (TC) (-69% vs -40%),
high density lipoprotein-cholesterol (HDL-C) (-49% vs -30%), and non-HDL-C (-81 vs -48%) concentrations; increased the activities of both
HMG-CoA reductase (1492% vs 62%) and
7 alpha-hydroxylase (175% vs 86%); lowered the concentration of hepatic
cholesteryl ester (-94% vs -59%); increased fecal
cholesterol concentration (+28% vs -10%); and decreased aortic fatty streak area (-100% vs -86%). Unexpected findings of this comparison were increased fecal concentrations of
cholic acid (533%) and
chenodeoxycholic acid (400%) and the reduction in
lithocholic acid (-50%) in the 0.6%
GT16-239 compared to the 1.2%
cholestyramine group. In summary,
GT16-239 had a greater impact on
cholesterol metabolism and early
atherosclerosis in hypercholesterolemic hamsters than
cholestyramine.