Different characteristics of chronic dibutyltin dichloride-induced pancreatitis and cholangitis in mouse and rat.

ABSTRACT

BACKGROUND: Current animal models of chronic pancreatitis (CP) often provide only limited pathophysiological insights since they incompletely reflect the human disease. CP induced by injection of dibutyltin dichloride (DBTC-pancreatitis) shares with human CP the important feature of extended fibrosis and would be an even more attractive model if it could be transferred from rats to mice, as recently suggested in the context of combined ethanol and DBTC application. This study aimed to evaluate the effects of DBTC in pancreas and liver of C57BL/6 mice, a strain commonly used to engineer genetic mouse models. METHODS: C57BL/6 mice and Lewis rats were exposed to variable doses of DBTC. After an investigation period of up to 4 weeks, laboratory findings and histopathological changes of pancreas and liver were evaluated. RESULTS: Chronic DBTC-pancreatitis in rats was characterized by acinar cell damage, ductal changes, fibrosis, and inflammatory cell infiltrates. Mice treated with DBTC at 6-8 mg/kg body weight, the standard doses in rats, showed transient increases of lipase activities but no morphological signs of chronic DBTC-pancreatitis 4 weeks after injection of the drug. Increased doses of 10-12 mg/kg DBTC were intolerable due to their high toxicity. In contrast, mice and rats presented with a similar histopathology of the liver that can be characterized as a chronic-proliferative DBTC-cholangitis with predominating damage and proliferation of the small bile ducts as well as secondary portal inflammatory cell infiltrates and a beginning portal fibrosis. CONCLUSIONS: The DBTC-model cannot be transferred from rats to C57BL/6 mice with respect to chronic DBTC-pancreatitis, but might be of interest to study DBTC-cholangitis in both species.