Functional, biochemical, and morphological hepatobiliary effects in rats chronically exposed to a steroidal antiandrogen

Toxicology and Applied Pharmacology
G DescotesC Moreau

Abstract

Yellow-brown deposits in intrahepatic bile ducts and portal macrophages were observed for male, but not female, Sprague- Dawley rats fed zanoterone, a steroidal antiandrogen, for >=3 months. The lesion did not affect biliary canaliculi and was associated with changes of biliary epithelium, portal chronic inflammation, and bile duct proliferation. Deposit formation was assumed to be related to a gender-related anomaly in bile composition and/or flow. Therefore, the pathogenesis of the lesion was investigated in male, female, and orchiectomized rat. Hepatobiliary structure and function were evaluated after 3 months of treatment and 3 months of reversibility. Drug biliary disposition was evaluated at 3 months. Sulfobromophthalein clearance, bile flow, and plasma concentration and biliary excretion rate of cholesterol were increased at the end of the treatment phase without significant sex-related differences. These effects are consistent with the hepatic enzyme induction potential of the drug, were accompanied by perivenous hepatocellular hypertrophy and increased liver weights, and were no longer observed at the end of the recovery phase. Histomorphologic evidence of cholestasis was observed for most intact and orchiectomized mal...Continue Reading

Citations

Mar 10, 2001·Clinics in Liver Disease·G A Kullak-Ublick, P J Meier
Jul 1, 2007·Environmental Toxicology and Pharmacology·Fen Xia HouWei Chen
Jan 31, 2002·World Journal of Gastroenterology : WJG·C StancaG A Kullak-Ublick
Dec 31, 2003·Gastroenterology·Gerd A Kullak-UblickPeter J Meier
Mar 19, 2002·Chemical Research in Toxicology·Deepak K DalvieJohn P O'Donnell

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