The protective role of natural phytoalexin resveratrol on inflammation, fibrosis and regeneration in cholestatic liver injury.
Abstract
Liver injuries can trigger a cascade of inflammatory responses and as a result, initiate the process of hepatic regeneration and fibrogenesis. Resveratrol (RSV) has multiple health-promoting benefits. This study evaluated the potential protective effects and mechanism of RSV as related to cholestatic liver injury. RSV was given (4 mg/kg/day, i.p.) for either 3 days or 7 days after bile duct ligation (BDL) injury. RSV significantly reduced serum ALT, AST but not T-bil on Day 3. At this early stage of injury, RSV significantly reduced TNF-α and IL-6 mRNA and decreased the number of Kupffer cells (CD68(+) ) recruited in the injured liver. RSV decreased hepatic fibrosis and reduced collagen Iα1 and TIMP-1 mRNA on Day 7. At the later stages of injury, RSV increased the number of Ki67(+) hepatocytes indicating that RSV promoted hepatocyte proliferation. Additionally, it resulted in decreased expression of 4-hydroxynonenal and increased expression of the hepatocyte growth factor protein and mRNA in the RSV-treated BDL group. Meanwhile, RSV reduced the mortality rate of BDL mice. In conclusion, RSV attenuated inflammation and reduced Kupffer cells activation. RSV decreased fibrosis and promoted hepatocyte regeneration, which increased the survival of BDL mice. RSV was beneficial for the treatment of cholestatic liver injury.
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Authors
Chan CC, Cheng LY, Lin CL, Huang YH, Lin HC, Lee FY
Institution
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Source
Molecular nutrition & food research 55:12 2011 Dec pg 1841-9MeSH
AldehydesAnimals
Bile Ducts
Cell Proliferation
Cholestasis
Collagen Type I
Hepatocytes
Inflammation
Interleukin-6
Kupffer Cells
Ligation
Liver Cirrhosis
Mice
Mice, Inbred C57BL
RNA, Messenger
Stilbenes
Tissue Inhibitor of Metalloproteinase-1
Tumor Necrosis Factor-alpha
Pub Type(s)
Journal ArticleResearch Support, Non-U.S. Gov't
Language
eng
PubMed ID
22086758
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