title: Regulation by resveratrol of the cellular factors mediating liver damage and regeneration after acute toxic liver injury.
abstract: OBJECTIVE
  Acute liver injury is manifested by different degree of hepatocyte necrosis and may recover via the process of hepatocyte regeneration once the injury is discontinued. Most of the liver injury is associating with inflammatory cytokines. Resveratrol (RSV) is a natural phytoalexin with powerful anti-inflammatory effects.
  
  
  OBJECTIVE
  The effects of RSV on cellular factors mediating liver damage and regeneration in acute carbon tetrachloride (CCl4 ) liver injury were investigated.
  
  
  RESULTS
  RSV decreased alanine aminotransferase, aspartate aminotransferase, necrosis, and 4-hydroxynonenal in the CCl4 -injured liver. RSV decreased hepatocyte apoptosis by reducing caspase 8 and caspase 3 but not Bax and Bcl-xL. RSV reduced Kupffer cells recruitment, the expressions of tumor necrosis factor-α and interleukin-6, but not interleukin-10. RSV lowered the numbers of anti-5-bromon-2'-deoxyuridine and anti-Ki67-positive hepatocytes. Hepatic hepatocyte growth factor, c-Met and transforming growth factor-α expressions were reduced by RSV, while transforming growth factor-β1 and hepatic stellate cells activation were not changed. RSV reduced the injury-induced CXCL10 elevations in serum and liver in vivo. Besides, RSV inhibited CXCL10 release from CCl4 -injured hepatocytes in vitro. In contrast, recombinant CXCL10 improved the viability of CCl4 -injured hepatocytes.
  
  
  CONCLUSIONS
  RSV therapy can be beneficial for acute toxic liver injury. RSV reduced hepatocyte apoptosis but limited hepatocyte regeneration possibly through reducing the hepatomitogenic signaling and the release of CXCL10.
authors: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University, School of Medicine, Institute of Clinical Medicine, Taipei, Taiwan.
authors: Che-Chang
authors: CC
authors: Chan
authors: Kuei-Chuan
authors: KC
authors: Lee
authors: Yi-Hsiang
authors: YH
authors: Huang
authors: Chung-Kai
authors: CK
authors: Chou
authors: Han-Chieh
authors: HC
authors: Lin
authors: Fa-Yauh
authors: FY
authors: Lee
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002251:Carbon Tetrachloride; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D054357:Chemokine CXCL10 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D008115:Liver Regeneration / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis / Q000188:drug therapy; D008517:Phytotherapy; D000077185:Resveratrol; D012717:Sesquiterpenes; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use*; D000094162:Phytoalexins
chemical_list: D000447:Aldehydes; D000893:Anti-Inflammatory Agents; D054357:Chemokine CXCL10; D016207:Cytokines; D018836:Inflammation Mediators; D012717:Sesquiterpenes; D013267:Stilbenes; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3; D053181:Caspase 8; C027576:4-hydroxy-2-nonenal; D000077185:Resveratrol; D000094162:Phytoalexins
keywords: CXCL10; apoptosis; cytokine; hepatocyte; regeneration; resveratrol