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The protective role of natural phytoalexin resveratrol on inflammation, fibrosis and regeneration in cholestatic liver injury
Author(s) -
Chan CheChang,
Cheng LingYi,
Lin ChinLung,
Huang YiHsiang,
Lin HanChieh,
Lee FaYauh
Publication year - 2011
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201100374
Subject(s) - hepatocyte , liver injury , resveratrol , fibrosis , liver regeneration , medicine , inflammation , cholestasis , immunology , regeneration (biology) , endocrinology , pharmacology , biology , biochemistry , in vitro , microbiology and biotechnology
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.