Bile duct hyperplasia

Dibutyltin dichloride induced acute pancreatitis and bile duct lesions in rats, depending on dose (6 and 8 mg/kg body weight intravenously) and time (1-24 weeks) (Merkord Hennighausen, 1989 Merkord et al., 1997, 1999 Sparmann et al., 2001). The lesions in the pancreas developed into a pancreatic fibrosis, and the lesions in the liver into liver cirrhosis. A single intravenous administration of dibutyltin dichloride at 4 mg/kg body weight induced a mild interstitial pancreatitis after 2 days (Merkord et al., 2001). Repeated administration of dibutyltin dichloride (4 mg/kg body weight intravenously) to rats at intervals of 3 weeks induced acute interstitial pancreatitis and, after 9-12 weeks, a pancreatic fibrosis and liver lesions (intrahepatic bile duct hyperplasia) (Merkord et al, 2001). 

Daqono, Sleight SD, Stowe HD, et al. 1983. Vitamin A status, polybrominated biphenyl (PBB) toxicosis, and common bile duct hyperplasia in rats. Toxicol Appl Pharmacol 71 184-193. 

In a 4-week feeding study in rats, it was only at dietary levels of 320 mg/kg bis(tributyltin)oxide that a low incidence of liver and bile duct changes were observed (Krajnc et al. 1984). The changes included atrophy of hepatocytes, necrotic areas (nonlobular), and bile duct hyperplasia. 

Also. -naphthylisothiocyanate (ANIT) enhances the measured HO activity. ANIT is a drug causing bile stasis, hyperbilirubinemia acutely, bile duct hyperplasia and biliary cirrhosis (Leonard et al. (1981), Ushida et al. (2002)). Therefore its HO activity enhancing potential is well known. 

Hepatic 2.0 M (hepatocellular 2.8 F hypertrophy and vacuolization, bile duct hyperplasia) ... 

Aroclor 1260 caused hepatocellular changes (hypertrophy, vacuohzation, altered foci), bile duct hyperplasia, and increased hver weight at 4.4 mg/kg/day, and increased serum GGT and cholesterol at... 

In rats orally administered 2.5 or 5 g/kg of Pu-erh green or Pu-erh black tea extract daily for 28 days, alanine aminotransferase increased in males at the 5 g/kg dose, and creatinine increased in all animals at the 5 g/kg dose and in males at the 2.5 g/kg dose. Slight bile duct hyperplasia in the liver was also observed. No adverse effects were observed in animals treated with Pu-erh black tea extract (Wang et al. 2010). 

Table 14. Liver Bile Duct Hyperplasia in Ducklings Fed Af la toxin...

Centrilobularfetty change and hepatocellular necrosis accompanied by moderate inleriob-ular fibrosis and bile duct hyperplasia in swine... 

IIF 1 bl. Aflatoxin inhibits protein synthesis in the liver and leads to diminished weight gain, liver dysfunction characterized by hepatocellular damage (indicated by both nonspecific and specific liver enzymes), and icterus as a result of both hepatocellular damage and bile retention associated with bile duct hyperplasia. 

The pattern of heptacellular damage describe is typical ofaflatoxin, including the distinct centrilobular pattern and the bile duct hyperplasia. Fumonisins are also hepatotoxic mycotoxins, but liver damage from fumonisins is typically mild to moderate and characterized by a more disorganized hepatic structure and little or no evidence of bile duct hyperplasia. 

Liver histopathology increased levels of minimal bile duct hyperplasia at all treatment levels... 

Ag 60 nm CMC Rat 6 weeks Oral gavage 30, 300, 1,000 mg/ kg b.w. per day 28 Normal b.w., food intake, organ weights Elevated blood cholesterol and AEP at mid- and high dose Eiver histopathology increased incidence of bile duct hyperplasia and inflammatory cell infiltration (dose and quantification not provided) Dose dependent stomach, liver, kidney, lung, testes, brain, blood Kidney Ag deposition more than twice as high in females than males (Kim et al. 2008)... 

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