Prevention of ursodeoxycholate hepatotoxicity in the rabbit by conjugation with N-methyl amino acids

✍ Scribed by Adrian Schmassmann; Alan F. Hofmann; M. Antonietta Angellotti; Huong-Thu Ton-Nu; Claudio D. Schteingart; Carlo Clerici; Steven S. Rossi; Marcus A. Rothschild; Bertram I. Cohen; Richard J. Stenger; Dr. Erwin H. Mosbach

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 836 KB
• Volume: 11
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840110613

✦ Synopsis

The effect of dietary administration of four different amino acid (N-acyl) conjugates of ursodeoxycholic acid on biliary bile acid composition, liver tests and hepatic morphology by light microscopy was examined in the rabbit. Each group of four to five rabbits received a chow diet supplemented with a single conjugate of ursodeoxycholic acid ursodeoxycholylglycine, ursodeoxycholyl-sarcosine, ursodeoxycholyltaurine or ursodeoxycholyl-N-methyltaurine for 3 wks at a dose of 50 madday; a control group received chow alone. After 3 wks of feeding, animals receiving ursodeoxycholyl-glycine or ursodeoxycholyl-taurine had hepatotoxicity associated with abnormal liver tests. Lithocholic acid made up 11% f 2.7% of biliary bile acids in the ursodeoxycholyl-glycine and 10% f 2.2% in the ursodeoxycholyl-taurine group. In contrast, animals receiving ursodeoxycholyl-sarcosine or ursodeoxycholyl-N-methyltaurine had neither hepatotoxicity nor abnormal liver tests and the proportion of lithocholic acid in biliary bile acids increased much less. Complementary studies showed that ursodeoxycholyl-sarcosine and ursodeoxycholyl-~