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

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...

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Autores principales: Kim, Kyung-Hyun, Sung, Hyun-Jung, Lee, Woo-Ram, An, Hyun-Jin, Kim, Jung-Yeon, Pak, Sok Cheon, Han, Sang-Mi, Park, Kwan-Kyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591642/
https://www.ncbi.nlm.nih.gov/pubmed/26308055
http://dx.doi.org/10.3390/toxins7093372
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author Kim, Kyung-Hyun
Sung, Hyun-Jung
Lee, Woo-Ram
An, Hyun-Jin
Kim, Jung-Yeon
Pak, Sok Cheon
Han, Sang-Mi
Park, Kwan-Kyu
author_facet Kim, Kyung-Hyun
Sung, Hyun-Jung
Lee, Woo-Ram
An, Hyun-Jin
Kim, Jung-Yeon
Pak, Sok Cheon
Han, Sang-Mi
Park, Kwan-Kyu
author_sort Kim, Kyung-Hyun
collection PubMed
description 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.
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spelling pubmed-45916422015-10-05 Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice Kim, Kyung-Hyun Sung, Hyun-Jung Lee, Woo-Ram An, Hyun-Jin Kim, Jung-Yeon Pak, Sok Cheon Han, Sang-Mi Park, Kwan-Kyu Toxins (Basel) Article 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. MDPI 2015-08-25 /pmc/articles/PMC4591642/ /pubmed/26308055 http://dx.doi.org/10.3390/toxins7093372 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Kyung-Hyun
Sung, Hyun-Jung
Lee, Woo-Ram
An, Hyun-Jin
Kim, Jung-Yeon
Pak, Sok Cheon
Han, Sang-Mi
Park, Kwan-Kyu
Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice
title Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice
title_full Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice
title_fullStr Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice
title_full_unstemmed Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice
title_short Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice
title_sort effects of melittin treatment in cholangitis and biliary fibrosis in a model of xenobiotic-induced cholestasis in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4591642/
https://www.ncbi.nlm.nih.gov/pubmed/26308055
http://dx.doi.org/10.3390/toxins7093372
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