Hepatic toxicity in the rhesus monkey treated with chenodeoxycholic acid for 6 months: biochemical and...

Area of Science:

• Hepatology
• Toxicology
• Gastroenterology

Background:

• Chenodeoxycholic acid (CDCA) administration requires caution due to observed liver damage in animal models.
• Understanding CDCA's dose-dependent effects on liver health is crucial for patient safety.

Purpose of the Study:

• To investigate the impact of varying CDCA doses on rhesus monkey liver function and morphology.
• To assess changes in biliary bile acid composition and the reversibility of induced liver damage.

Main Methods:

• 22 rhesus monkeys were administered CDCA at doses of 10, 40, or 100 mg/kg/day for 6 months.
• Hepatic function, morphology, and biliary bile acid profiles were analyzed.
• Reversibility was assessed after a 3-month withdrawal period.

Main Results:

• High CDCA doses (40 and 100 mg/kg/day) induced bile duct proliferation, portal inflammation, fibrosis, and smooth endoplasmic reticulum hypertrophy.
• Elevated liver enzymes (AST, ALT, LAP) were observed in high-dose groups.
• Bile composition shifted, with increased CDCA and lithocholic acid; these changes normalized post-withdrawal, but histological lesions persisted in some animals.
• The 10 mg/kg/day dose did not cause hepatic abnormalities.

Conclusions:

• High-dose, long-term CDCA treatment causes severe, persistent liver histological lesions in rhesus monkeys.
• These findings highlight the potential risks associated with prolonged CDCA use, even after cessation.
• Lower CDCA doses may be tolerated without adverse hepatic effects.