Dissolution of cholesterol gallstones by bile acids in hamsters.
We previously reported a hamster model for cholesterol gallstone formation and prophylaxis. The aim of this study was to validate a model for dissolution of cholesterol gallstones by testing bile acids used in patients. Sixty hamsters were allocated to six groups of ten; Group I received the standard diet (.8mg cholesterol/gram food) and Groups II-VI received the lithogenic regime (2.4 mg cholesterol/gram food and 15 micrograms ethinyl estradiol) for twelve weeks. During the next eight weeks, Group I remained on the standard diet, Group II on the lithogenic regime, while Group III switched to the standard diet. Groups IV-VI remained on the lithogenic regime, and received 20 mg/kg/d of CDC (Group IV), UDC (Group V) or cholic acid (Group VI). Cholesterol gallstones were found in 90% of hamsters on the lithogenic regime, even after return to the standard diet, in 80% of those receiving cholic acid, and in none receiving the standard diet, CDC or UDC. CDC and UDC but not cholic acid inhibited hepatic HMG-CoA reductase activity (p less than 0.01) and desaturated bile (p less than 0.01). The highest HMG-CoA reductase (p less than 0.02) occurred after return from the lithogenic regime to the standard diet.


CONCLUSIONS
1) A new model for cholesterol gallstone dissolution has been validated; 2) CDC and UDC, in contrast to cholic acid, decreased HMG-CoA reductase, desaturated bile and dissolved gallstones as in patients; and 3) Return from the lithogenic regime to the standard diet did not desaturate bile or dissolve gallstones, but did increase HMG-CoA reductase as found in gallstone patients.
D000818:Animals; D001647:Bile Acids and Salts / Q000627:therapeutic use*; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage; D002769:Cholelithiasis / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D002793:Cholic Acids / Q000008:administration & dosage; D006224:Cricetinae; D004195:Disease Models, Animal; D004997:Ethinyl Estradiol / Q000008:administration & dosage; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000032:analysis; D008099:Liver / Q000201:enzymology; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage
D001647:Bile Acids and Salts; D002793:Cholic Acids; D002635:Chenodeoxycholic Acid; D004997:Ethinyl Estradiol; D014580:Ursodeoxycholic Acid; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases