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Regulation by resveratrol of the cellular factors mediating liver damage and regeneration after acute toxic liver injury
Author(s) -
Chan CheChang,
Lee KueiChuan,
Huang YiHsiang,
Chou ChungKai,
Lin HanChieh,
Lee FaYauh
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12366
Subject(s) - hepatocyte , liver injury , liver regeneration , medicine , resveratrol , tumor necrosis factor alpha , necrosis , ccl4 , pharmacology , immunology , regeneration (biology) , cancer research , carbon tetrachloride , biology , pathology , chemistry , in vitro , microbiology and biotechnology , biochemistry , organic chemistry
Abstract Background and Aim 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. Aim The effects of RSV on cellular factors mediating liver damage and regeneration in acute carbon tetrachloride ( CCl 4 ) liver injury were investigated. Results RSV decreased alanine aminotransferase, aspartate aminotransferase, necrosis, and 4‐hydroxynonenal in the CCl 4 ‐injured liver. RSV decreased hepatocyte apoptosis by reducing caspase 8 and caspase 3 but not Bax and Bcl‐xL . RSV reduced K upffer 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‐ K i67‐positive hepatocytes. Hepatic hepatocyte growth factor, c‐ M et 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 CXCL 10 elevations in serum and liver in vivo . Besides, RSV inhibited CXCL 10 release from CCl 4 ‐injured hepatocytes in vitro . In contrast, recombinant CXCL 10 improved the viability of CCl 4 ‐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 CXCL 10.