Antilithiasic effect of beta-cyclodextrin in LPN hamster: comparison with cholestyramine

beta-Cyclodextrin (BCD), a cyclic oligosaccharide that binds cholesterol an d bile acids in vitro, has been previously shown to be an effective plasma cholesterol lowering agent in hamsters and domestic pigs, This study examin ed the effects of BCD as compared with cholestyramine on cholesterol and bi le acid metabolism in the LPN hamster model model for cholesterol gallstone s, The incidence of cholesterol gallstones was 65% in LPN hamsters fed the lithogenic diet, but decreased linearly with increasing amounts of BCD in t he diet to be niI at a dose of 10% BCD. In gallbladder bile, cholesterol, p hospholipid and chenodeoxycholate concentrations, hydrophobic and lithogeni c indices were all significantly decreased by 10% BCD. Increases in bile ac id synthesis (+110%), sterol 27-hydroxylase activity (+106%), and biliary c holate secretion (+140%) were also observed, whereas the biliary secretion of chenodeoxycholate decreased (-43%). The fecal output of chenodeoxycholat e and cholate (plus derivatives) was increased by +147 and +64%, respective ly, suggesting that BCD reduced the chenodeoxycholate intestinal absorption preferentially. Dietary cholestyramine decreased biliary bile acid concent ration and secretion, but dramatically increased the fecal excretion of che nodeoxycholate and cholate plus their derivatives (+328 and +1940%, respect ively), In contrast to BCD, the resin increased the lithogenic index in bil e, induced black gallstones in 34% of hamsters, and stimulated markedly the activities of HMG-CoA reductase (+670%), sterol 27-hydroxylase (-310%), an d cholesterol 7 alpha-hydroxylase (+390%). Thus, beta-cyclodextrin (BCD) pr evented cholesterol gallstone formation by decreasing specifically the reab sorption of chenodeoxycholate, stimulating its biosynthesis and favoring it s fecal elimination. BCD had a milder effect on lipid metabolism than chole styramine and does not predispose animals to black gallstones as cholestyra mine does in this animal model.