Toxicity of chenodeoxycholic acid in the rhesus monkey.
Chenodeoxycholic acid is an important drug for the treatment of cholesterol cholelithiasis in man. Although no toxicity has been demostrated in man, liver lesions develop in rhesus monkeys treated with chenodeoxycholic acid. To elucidate the mechanism of toxicity, chenodeoxycholic acid. To elucidate the mechanism of toxicity, chenodeoxycholic acid was fed daily to three groups of 6 animals each at the following dose: 10, 40, and 100 mg per kg; 2 separate animals were not treated and served as controls. After 1 month, the animals were killed. During the treatment period, most blood tests (e.g., blood count, blood urea nitrogen, albumin, SGOT, lactate dehydrogenase) remained within normal limits, but there was a significant dose-related increase in serum leucine aminopeptidase levels. The percentage of lithochlic acid, the 7-dehydroxylated bacterial metabolite of chenodeoxycholic acid, rose from 1% in the control animal to almost 14% in the 100 mg per kg-treated group. Liver biopsies obtained before treatment and at necropsy showed no significant changes. Thus, exposure of the liver to increased amounts of lithocholic acid during chenodeoxycholic acid treatment might result in elevation of serum leucine aminopeptidase activity.
D000818:Animals; D001646:Bile / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D002769:Cholelithiasis / Q000188:drug therapy; D002784:Cholesterol / Q000032:analysis; D002793:Cholic Acids / Q000032:analysis; D003840:Deoxycholic Acid / Q000032:analysis; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D007931:Leucyl Aminopeptidase / Q000097:blood; D008095:Lithocholic Acid / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D010743:Phospholipids / Q000032:analysis
D002793:Cholic Acids; D010743:Phospholipids; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D008095:Lithocholic Acid; D002784:Cholesterol; D007931:Leucyl Aminopeptidase