Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/18234
Title: The small molecule drug diminazene aceturate inhibits liver injury and biliary fibrosis in mice.
Austin Authors: Rajapaksha, Indu G;Mak, Kai Yan;Huang, Ping;Burrell, Louise M ;Angus, Peter W ;Herath, Chandana B
Affiliation: Medicine (University of Melbourne)
Gastroenterology and Hepatology
Issue Date: 5-Jul-2018
Date: 2018-07-05
Publication information: Scientific Reports 2018; 8(1): 10175
Abstract: There is no established medical therapy to treat biliary fibrosis resulting from chronic inflammation in the biliary tree. We have recently shown that liver-specific over-expression of angiotensin converting enzyme 2 (ACE2) of the renin angiotensin system (RAS) ameliorated liver fibrosis in mice. Diminazene aceturate (DIZE), a small molecule drug approved by the US Food and Drug Administration, which is used to treat human trypanosomiasis, has been shown to have antifibrotic properties by enhancing ACE2 activity. In this study we sought to determine the therapeutic potential of DIZE in biliary fibrosis using bile duct ligated and multiple drug resistant gene-2 knockout mice. Additionally, human hepatic stellate (LX-2) and mouse Kupffer (KUP5) cell lines were used to delineate intracellular pathways. DIZE treatment, both in vivo and in vitro, markedly inhibited the activation of fibroblastic stellate cells which was associated with a reduced activation of Kupffer cells. Moreover, DIZE-inhibited NOX enzyme assembly and ROS generation, activation of profibrotic transcription factors including p38, Erk1/2 and Smad2/3 proteins and proinflammatory and profibrotic cytokine release. These changes led to a major reduction in biliary fibrosis in both models without affecting liver ACE2 activity. We conclude that DIZE has a potential to treat biliary fibrosis.
URI: https://ahro.austin.org.au/austinjspui/handle/1/18234
DOI: 10.1038/s41598-018-28490-y
ORCID: 0000-0002-4403-7177
0000-0003-1863-7539
Journal: Scientific Reports
PubMed URL: 29977014
Type: Journal Article
Appears in Collections:Journal articles

Show full item record

Page view(s)

42
checked on Mar 28, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.