gamma-sitosterol and Cholelithiasis

Quantitative analysis of the local distribution of four noncholesterol sterols, 24-methylene cholesterol, campesterol, stigmasterol, and beta-sitosterol, and of the local distribution of cholesterol in gallstones was performed by mass spectrometry, with D6-cholesterol as an internal standard. The role played by trace amounts of these four noncholesterol sterols in the formation of gallstones was investigated by comparing the amounts of these sterols in different parts of gallstones. It was found that the amounts of the noncholesterol sterols in the inside part were significant greater than the amounts in the outside part of various structural types of gallstones. However, the distribution of the cholesterol did not show such variation. The amounts of noncholesterol sterols distributed locally suggested that these sterols play a role in the formation of gallstones.

Topics: Cholelithiasis; Cholesterol; Female; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Phytosterols; Sitosterols; Sterols; Stigmasterol

The effect of various dietary additions such as cholesterol, beta-sitosterol, bile acids, and bile acid analogs on gallstone formation was studied in the hamster. Gallstones were formed in 50% of the animals fed a high glucose, fat-free diet. Administration of 0.2% cholesterol or 1% beta-sitosterol had no effect on the incidence of gallstones. Ursodeoxycholic acid (0.5%) and its analog ursodeoxy-oxazoline [2-(3 alpha, 7 beta-dihydroxy-24-nor-5 beta-cholanyl)-4,4-dimethyl-2- oxazoline] were ineffective in preventing gallstones. Hyodeoxycholic acid and hyodeoxy-oxazoline [2-(3 alpha,6 alpha-dihydroxy-24-nor-5 beta-cholanyl)-4,4-dimethyl-2- oxazoline] at the same dosage effectively prevented gallstones, while the trihydroxy bile acid, hyocholic acid, was not effective. Of all the dietary regimens tested, only hyodeoxycholic acid significantly lowered serum cholesterol. The lithogenic diet produced a five-fold increase in hepatic HMG-CoA reductase activity; this activity was not affected by dietary cholesterol or beta-sitosterol. Hyodeoxycholic acid and hyocholic acid feeding increased the reductase activity by an additional 50% while the other bile acids had no effect. beta-Sitosterol doubled the cholesterol 7 alpha-hydroxylase activity whereas hyodeoxy-oxazoline lowered it. Hyodeoxycholic acid-fed animals had significantly lower cholesterol absorption than the animals on the lithogenic diet alone. Biliary cholesterol content increased dramatically in the animals fed the lithogenic diet and was increased still further by ursodeoxycholic acid, hyodeoxycholic acid, and hyodeoxy-oxazoline. These data show that hyodeoxycholic acid and hyodeoxy-oxazoline do not prevent gallstones by inhibiting hepatic cholesterol synthesis or biliary cholesterol secretion.

Topics: Animals; Bile; Bile Acids and Salts; Cholanes; Cholelithiasis; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Cholic Acids; Cricetinae; Deoxycholic Acid; Diet; Hydroxymethylglutaryl CoA Reductases; Liver; Male; Mesocricetus; Phospholipids; Sitosterols; Sterols; Ursodeoxycholic Acid