[Correlation of biliary cholesterol, phospholipids and bile acid compositions and the development of cholesterol cholelithiasis in mice].
A study was attempted to establish a screening method for detecting cholelitholytic ingredients from a wide variety of natural substances. Although mice were selected as a suitable pathological model of cholelithiasis to detect a small amount of the ingredients, all the conventional lithogenic diets caused unfavorable influence on the animals. Therefore, as the first step we formulated a new lithogenic diet consisting of butter, cholesterol, cholic acid, etc, which was adequate for mice. Subsequently, the pathological characteristics and persistence of cholelithiasis were examined in the animals; the changes in bile compositions including free and conjugated bile acids, cholesterol and phospholipids were observed before and at the onset of cholelithiasis. Following confirmation of the stone formation, a normal diet was substituted for the lithogenic diet to likewise assess the bile compositions 4 and 6 weeks later. An increasing tendency for deoxycholic acid, disappearance of chenodeoxycholic acid and decrease in ursodeoxycholic acid were seen under the condition of cholelithiasis. In addition, the cholic acid-glycine conjugate which should not exist in the normal state and the increase in free and tauring-conjugated cholic acid were noticed. The biliary cholesterol level in treated mice increased to about 4 times higher than that in untreated mice, while the biliary phospholipids and total bile acids levels increased to only about 1.5 and about 2 times the control levels, respectively. The incidence of stone formation rose sharply at an experimental period between 2 and 3 weeks after starting the lithogenic diet. Gallstones die not disappear even at the 6th week after substituting a normal diet for the lithogenic one. However, the cholic acid-glycine conjugate disappeared, and deoxycholic acid as well as chenodeoxycholic acid and ursodeoxycholic acid tended to recover to the normal levels in the bile.
D000818:Animals; D001646:Bile / Q000032:analysis*; D001647:Bile Acids and Salts / Q000032:analysis*; D002635:Chenodeoxycholic Acid / Q000032:analysis; D002769:Cholelithiasis / Q000209:etiology* / Q000378:metabolism; D002784:Cholesterol / Q000032:analysis*; D003840:Deoxycholic Acid / Q000032:analysis; D008297:Male; D051379:Mice; D010743:Phospholipids / Q000032:analysis*; D014580:Ursodeoxycholic Acid / Q000032:analysis
D001647:Bile Acids and Salts; D010743:Phospholipids; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; D002784:Cholesterol