Prevention of ursodeoxycholate hepatotoxicity in the rabbit by conjugation withN-methyl amino acids
| Autor: | B I Cohen, Steven S. Rossi, Marcus A. Rothschild, Alan F. Hofmann, Carlo Clerici, Adrian Schmassmann, H.-T. Ton-Nu, Richard J. Stenger, Claudio D. Schteingart, E H Mosbach, M. Antonietta Angellotti |
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| Rok vydání: | 1990 |
| Předmět: |
Male
medicine.medical_specialty Lithocholic acid medicine.drug_class Guinea Pigs Biology Bile Acids and Salts chemistry.chemical_compound Oral administration Internal medicine medicine Animals Amino Acids Biotransformation chemistry.chemical_classification Hepatology Bile acid Body Weight Ursodeoxycholic Acid Ursodeoxycholate Organ Size Ursodeoxycholic acid Diet Amino acid Cholesterol Endocrinology Liver chemistry Toxicity Bile Ducts Rabbits Deoxycholic Acid medicine.drug |
| Zdroj: | Hepatology. 11:989-996 |
| ISSN: | 1527-3350 0270-9139 |
| Popis: | 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 mg/kg/day; 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% ± 2.7% of biliary bile acids in the ursodeoxycholyl-glycine and 10% ± 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-N-methyltaurine were not biotransformed during hepatic transport and were resistant to deconjugation and dehydroxylation in the rabbit. These experiments indicate that the N-methyl amino acid conjugates of ursodeoxycholic acid are nontoxic in the rabbit and resist deconjugation and dehydroxylation. Such resistance decreases formation of lithocholic acid in the colon, thus reducing its accumulation and consequent induction of hepatotoxicity.(HEPATOLOGY 1990;11:989-996.). |
| Databáze: | OpenAIRE |
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