Hamsters fed a lithogenic diet become hyperlipemic with elevated
very-low-density lipoprotein (VLDL) and
high-density lipoprotein 2 (
HDL2) cholesterol pools and develop lithogenic bile in which
chenodeoxycholate (cheno) typically predominates. The relationship between these distorted
lipoprotein and bile
lipid profiles and
gallstone induction was investigated in male Syrian hamsters fed for 5 weeks a
gallstone-inducing purified diet (5% butter, 0.4%
cholesterol) or the same diet supplemented with 5%
psyllium or 1%
cholestyramine, agents known to alter
bile acid metabolism. The
gallstone diet essentially doubled plasma
cholesterol level, whereas
psyllium decreased it to near normal, and
cholestyramine to a subnormal level, while correcting the distorted distribution of
cholesterol among
lipoproteins. Both the
gallstone diet and
psyllium produced
cholesterol-laden livers, in contrast to subnormal values produced by
cholestyramine. Fecal
bile acid excretion was increased eightfold with
cholestyramine and fourfold with
psyllium relative to the value produced by the
gallstone diet and a literature control value. Supersaturated bile developed with the
gallstone diet (lithogenic index [LI], 2.3 +/- 0.6), whereas the LI was decreased by
psyllium (1.2 +/- 0.4) and
cholestyramine (0.7 +/- 0.3). The
gallstone diet decreased the concentration of
bile acids in gallbladder bile, but greatly increased the percentage of
taurochenodeoxycholic acid, whereas
psyllium preferentially decreased all
taurine-conjugated
bile acid levels and expanded
glycocholate output.
Cholestyramine greatly decreased the secretion of biliary
cholesterol and cheno independent of its conjugation. Accordingly,
psyllium increased the
glycine to
taurine ratio of gallbladder bile fivefold, whereas
cholestyramine did not affect this ratio, but increased the
cholate to cheno ratio dramatically (25-fold) as compared with a threefold increase with
psyllium. This combination of biliary
lipid and
bile acid alterations induced coordinated responses in the LI and the hydrophobicity index (HI) such that
cholesterol gallstones developed in 11 of 12 hamsters fed the
gallstone diet, whereas only one of 11 of the
psyllium-fed and none of 12
cholestyramine-fed hamsters had
cholesterol stones. Thus,
psyllium and
cholestyramine differentially increased
bile acid excretion, which improved the
lipoprotein profile and inhibited
cholesterol gallstone formation. Both agents operated by different means to decrease biliary
cholesterol secretion and the percentage of cheno, which decreased the LI and HI, respectively.