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Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice

Department of Pathology, College of Medicine, Catholic University of Daegu, 3056-6, Daemyung-4-Dong, Nam-gu, Daegu 705-718, Korea
School of Biomedical Sciences, Charles Sturt University, Panorama Avenue, Bathurst, NSW 2795, Australia
Department of Agricultural Biology, National Academy of Agricultural Science, RDA, 300, Nongsaengmyeong-ro, Wansan-gu, Jeonju-si, Jeollabuk-do 55365, Korea
Author to whom correspondence should be addressed.
Academic Editor: Ren Lai
Toxins 2015, 7(9), 3372-3387;
Received: 23 June 2015 / Revised: 13 August 2015 / Accepted: 20 August 2015 / Published: 25 August 2015
PDF [3249 KB, uploaded 25 August 2015]


Cholangiopathy is a chronic immune-mediated disease of the liver, which is characterized by cholangitis, ductular reaction and biliary-type hepatic fibrosis. There is no proven medical therapy that changes the course of the disease. In previous studies, melittin was known for attenuation of hepatic injury, inflammation and hepatic fibrosis. This study investigated whether melittin provides inhibition on cholangitis and biliary fibrosis in vivo. Feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to mice is a well-established animal model to study cholangitis and biliary fibrosis. To investigate the effects of melittin on cholangiopathy, mice were fed with a 0.1% DDC-containing diet with or without melittin treatment for four weeks. Liver morphology, serum markers of liver injury, cholestasis markers for inflammation of liver, the degree of ductular reaction and the degree of liver fibrosis were compared between with or without melittin treatment DDC-fed mice. DDC feeding led to increased serum markers of hepatic injury, ductular reaction, induction of pro-inflammatory cytokines and biliary fibrosis. Interestingly, melittin treatment attenuated hepatic function markers, ductular reaction, the reactive phenotype of cholangiocytes and cholangitis and biliary fibrosis. Our data suggest that melittin treatment can be protective against chronic cholestatic disease in DDC-fed mice. Further studies on the anti-inflammatory capacity of melittin are warranted for targeted therapy in cholangiopathy. View Full-Text
Keywords: cholangiopathy; melittin; DDC-fed mice cholangiopathy; melittin; DDC-fed mice

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Kim, K.-H.; Sung, H.-J.; Lee, W.-R.; An, H.-J.; Kim, J.-Y.; Pak, S.C.; Han, S.-M.; Park, K.-K. Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice. Toxins 2015, 7, 3372-3387.

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