Comparative effects of deoxycholate and 7-methyl-deoxycholate in the hamster.
The metabolism and effect on biliary lipids of a new bile acid analog, 7-methyl-deoxycholic acid, were studied and compared with those of deoxycholic acid in the hamster. 14C-Labeled 7-methyl-deoxycholic acid and deoxycholic acid were administered intravenously or intraduodenally to bile fistula hamsters at 1.0 or 4.0 mumoles per min X kg, and hepatic bile was analyzed for radioactive metabolites and biliary lipid outputs. Deoxycholic acid and 7-methyl-deoxycholic acid were efficiently absorbed from the intestine, extracted by the liver and excreted into bile as taurine and glycine conjugates. Twenty per cent of deoxycholic acid was 7 alpha-hydroxylated to cholic acid while 7-methyl-deoxycholic acid did not undergo hydroxylation. During deoxycholic acid infusion, the biliary secretion of phospholipid did not increase, and the bile became more lithogenic. In contrast, 7-methyl-deoxycholic acid stimulated phospholipid secretion, and bile became less lithogenic. Although pathologic changes in the liver were inconstant and mostly mild, both bile acids were toxic in the hamster; hemolysis and death due to respiratory distress were observed.
D000818:Animals; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D001711:Biotransformation; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D003840:Deoxycholic Acid / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D008647:Mesocricetus
D001647:Bile Acids and Salts; D003840:Deoxycholic Acid; C051982:7-methyldeoxycholic acid; D002784:Cholesterol