title: 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.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Che-Chang
authors.initials: CC
authors.lastname: Chan
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Cheng
authors.forename: Chin-Lung
authors.initials: CL
authors.lastname: Lin
authors.forename: Yi-Hsiang
authors.initials: YH
authors.lastname: Huang
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
authors.forename: Fa-Yauh
authors.initials: FY
authors.lastname: Lee
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001652:Bile Ducts / Q000473:pathology / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D002779:Cholestasis / Q000188:drug therapy*; D024042:Collagen Type I / Q000187:drug effects / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008026:Ligation; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D000447:Aldehydes; D024042:Collagen Type I; D015850:Interleukin-6; D012333:RNA, Messenger; D013267:Stilbenes; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; C027576:4-hydroxy-2-nonenal; D000077185:Resveratrol