Alterations of mast cells and TGF-beta1 on the silymarin treatment for CCl(4)-induced hepatic fibrosis.
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.
Jeong
Da-Hee
DH
College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
Lee
Gi-Ppeum
GP
Jeong
Won-Il
WI
Do
Sun-Hee
SH
Yang
Hai-Jie
HJ
Yuan
Dong-Wei
DW
Park
Ho-Yong
HY
Kim
Kyu-Jong
KJ
Jeong
Kyu-Shik
KS
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
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