Background:Current animal models of chronic pancreatitis(CP)often provide only limited pathophysio-logical insights since they incompletely reflect the human disease.CP induced by injection of dibutyltin dichloride(DB...Background:Current animal models of chronic pancreatitis(CP)often provide only limited pathophysio-logical 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 sug-gested 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 mod-els.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,fi-brosis,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 begin-ning 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.展开更多
文摘Background:Current animal models of chronic pancreatitis(CP)often provide only limited pathophysio-logical 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 sug-gested 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 mod-els.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,fi-brosis,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 begin-ning 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.
