title: Alterations of mast cells and TGF-beta1 on the silymarin treatment for CCl(4)-induced hepatic fibrosis.
abstract: OBJECTIVE
  Silymarin is a potent antioxidant, antiinflammatory and anti-fibrogenic agent in the liver, which is mediated by alteration of hepatic Kupffer cell function, lipid peroxidation, and collagen production. Especially, in hepatic fibrogenesis, mast cells are expressed in chronic inflammatory conditions, and promote fibroblast growth and stimulate production of the extracellular matrix by hepatic stellate cells.
  
  
  METHODS
  We examined the inhibitory mechanism of silymarin on CCl(4)-induced hepatic cirrhosis in rats. At 4, 8, and 12 wk, liver tissues were examined histopathologically for fibrotic changes produced by silymarin treatment.
  
  
  RESULTS
  In the silymarin with CCl(4)-treated group, increase of hepatic stellate cells and TGF-beta1 production were lower than in the CCl(4)-treated group at early stages. Additionally, at the late fibrogenic stage, expressions of TGF-beta1 were weaker and especially not expressed in hepatocytes located in peripheral areas. Moreover, the number of mast cell in portal areas gradually increased and was dependent on the fibrogenic stage, but those of CCl(1)+silymarin-treated group decreased significantly.
  
  
  CONCLUSIONS
  Anti-fibrotic and antiinflammatory effects of silymarin were associated with activation of hepatic stellate cells through the expression of TGF-beta1 and stabilization of mast cells. These results suggest that silymarin prevent hepatic fibrosis through suppression of inflammation and hypoxia in the hepatic fibrogenesis.
authors.affiliation: College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Da-Hee
authors.initials: DH
authors.lastname: Jeong
authors.forename: Gi-Ppeum
authors.initials: GP
authors.lastname: Lee
authors.forename: Won-Il
authors.initials: WI
authors.lastname: Jeong
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Do
authors.forename: Hai-Jie
authors.initials: HJ
authors.lastname: Yang
authors.forename: Dong-Wei
authors.initials: DW
authors.lastname: Yuan
authors.forename: Ho-Yong
authors.initials: HY
authors.lastname: Park
authors.forename: Kyu-Jong
authors.initials: KJ
authors.lastname: Kim
authors.forename: Kyu-Shik
authors.initials: KS
authors.lastname: Jeong
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
chemical_list: D000975:Antioxidants; D012838:Silymarin; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase