title: 7-Methyl bile acids: effects of chenodeoxycholic acid, cholic acid, and their 7 beta-methyl analogues on the formation of cholesterol gallstones in the prairie dog.
abstract: The purpose of this study was to compare the effects of the naturally occurring bile acids (chenodeoxycholic acid and cholic acid) with their 7-methyl analogues (3 alpha,7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic acid and 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta-methyl-5 beta-cholanoic acid) on gallstone formation and prevention and cholesterol metabolism in the prairie dog. Sixty animals were fed a semipurified diet, containing 0.4% cholesterol, with one of the following acids (0.1%): chenodeoxycholic, cholic, 3 alpha,7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic, or 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta-methyl-5 beta-cholanoic acid. This concentration of dietary bile acids amounts to a dose of 27-30 mg/kg.day. After 8 wk, 89% of control animals had gallstones and 94% had cholesterol crystals. Chenodeoxycholic and 3 alpha,7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic acids decreased the incidence of gallstones to 50%. Cholic acid and 3 alpha,7 alpha,12 alpha-tri-hydroxy-7 beta-methyl-5 beta-cholanoic acid did not prevent gallstone formation. The liver cholesterol level was decreased by chenodeoxycholic acid, whereas cholic and 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta-methyl-5 beta-cholanoic acids increased serum and liver cholesterol. Each administered bile acid became the predominant biliary bile acid and 7-methyl analogues did not increase secondary bile acids. Fecal analysis of radioactive metabolites using 14C-labeled 7-methyl analogues showed that these compounds are resistant to bacterial 7-dehydroxylation. It was concluded that 3 alpha,7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic acid inhibited gallstone formation as effectively as chenodeoxycholic acid, whereas both cholic and 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta-methyl-5 beta-cholanoic acids were not effective. The effects of 7-methyl analogues on the parameters of cholesterol metabolism that we studied were similar to those of their parent compounds, chenodeoxycholic and cholic acids. Thus, 3 alpha,7 alpha-dihydroxy-7 beta-methyl-5 beta-cholanoic acid but not 3 alpha,7 alpha,12 alpha-trihydroxy-7 beta-methyl-5 beta-cholanoic acid offers promise in cholelitholytic therapy for the prevention and possibly dissolution of cholesterol gallstones.
authors.affiliation: Department of Surgery, Beth Israel Medical Center, New York, New York.
authors.forename: N
authors.initials: N
authors.lastname: Matoba
authors.forename: B I
authors.initials: BI
authors.lastname: Cohen
authors.forename: E H
authors.initials: EH
authors.lastname: Mosbach
authors.forename: R J
authors.initials: RJ
authors.lastname: Stenger
authors.forename: S
authors.initials: S
authors.lastname: Kuroki
authors.forename: M
authors.initials: M
authors.lastname: Une
authors.forename: C K
authors.initials: CK
authors.lastname: McSherry
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000494:pharmacology*; D002769:Cholelithiasis / Q000378:metabolism / Q000503:physiopathology*; D002784:Cholesterol / Q000378:metabolism; D019826:Cholic Acid; D002793:Cholic Acids / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D012589:Sciuridae; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D001647:Bile Acids and Salts; D002793:Cholic Acids; D010743:Phospholipids; D002635:Chenodeoxycholic Acid; C051656:3,7,12-trihydroxy-7-methylcholanoic acid; D014580:Ursodeoxycholic Acid; C041636:3,7-dihydroxy-7-methylcholanoic acid; D002784:Cholesterol; D019826:Cholic Acid