Gallstones cholestanol

These results were confirmed by Caira et al. (85,133), who found gallstones in New Zealand rabbits of both sexes fed 0.5 g cholestanol for 9 days or more. They observed that the newly formed stones were gelatinous in consistency and were accompanied by marked mucosal inflammatory changes (edema, round cell infiltration, and fibrosis). Choledocholithiasis developed readily in cholecystectomized animals, indicating that the liver bile itself was abnormal and that a gallbladder was not essential for stone formation. Similar concretions formed in two of 20 guinea pigs fed 0.25 g cholestanol daily, but none formed in rats fed 0.125 g daily. 

Mosbach and Bevans (134) showed that cholestanol-induced cholecystitis and cholelithiasis could be inhibited by the simultaneous administration of dehydrocholic acid and that the extent of inhibition depended on the relative concentrations of the two steroids. Similar observations were made by Ricci et al, (135). Deoxycholic and cholic acids were also effective inhibitors (136), but hyodeoxycholic acid did not suppress gallstone formation and appeared to increase biliary tract inffammation. Several non-bile acid choleretics were without inhibitory effects (136). Lindelof and van der Linden (32) found that intravenous injections of cholecystokinin every 8 hr did not suppress and may actually have enhanced gallstone formation. The inhibition of cholelithiasis by dehydrocholic, deoxycholic, and cholic acids was not accompanied by a decrease in cholestanol absorption but did result in increased tissue cholestanol levels, suggesting a decrease in the conversion of this sterol to bile acids (134,136). Conversely, methyl testosterone apparently inhibited stone formation by interfering with cholestanol absorption, since tissue and serum levels of cholestanol were reduced (137). Olive oil has been shown to facilitate stone formation (138), perhaps by enhancing cholestanol absorption (137). 

Early studies on the composition of cholestanol-induced gallstones established that they did not contain appreciable amounts of sterol (cholesterol or cholestanol) or pigment but consisted largely of glycine-conjugated bile salts (130,133,139,140). Mosbach and Bevans (139), utilizing cholestanol-14C, demonstrated that approximately half of the bile acids in the stones were... 

The natural occurrence of the 5a-epimer of deoxycholic acid was first demonstrated by Danielsson, Kallner, and Sjovall (62). The original isolation of this compound was probably by Kishi (61) who named the unidentified acid lagodeoxycholic acid from rabbit bile. In addition to its occurrence in rabbit bile, allodeoxycholic acid is present in rabbit feces (62) and accumulates as the glycine conjugate in gallstones of rabbits fed cholestanol (168). Allodeoxycholic acid may be synthesized from cholic acid by reactions similar to the preparation of allocholic acid (62,168). 

Hofmann and Mosbach (36) have identified allodeoxycholic acid as the conjugate with glycine in gallstones from rabbits fed a diet of 1 % cholestanol. Subsequent experiments have confirmed the origin of allodeoxycholic acid in this species from allocholic acid by intestinal dehydroxylation at (123) the intestinal anaerobe capable of this reaction in the rabbit has been characterized (38). 

PROBLEM 5.48 Cholestanol (shown below) is a natural product found in gallstones and eggs. How many stereogenic atoms are there in this molecule Draw the compound with the rings in their most stable conformation. Hint The molecule is relatively flat when viewed in three dimensions. 

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