Effects of carbon tetrachloride-injured hepatocytes on hepatic stellate cell activation and salvianolic acid A preventive action in vitro.
OBJECTIVE
To investigate the effects of carbon tetrachloride (CCl(4))-injured hepatocyte on hepatic stellate cell (HSC) activation, the relation between lipid peroxidation and liver fibrosis, and the action mechanisms of salvianolic acid A (SA-A), one of water soluble components extracted from radix salvia miltiorrhizae, against HSC activation and liver fibrosis.


METHODS
The hepatocytes were isolated from the normal rats, incubated with SA-A at different concentrations, respectively, and vitamin E severed as control. At the same time the cells were fumigated with CCl(4) for 24h, and ALT activities in the medium were measured. After the cell medium was changed and cultured for another 24h, the medium was collected as "hepatocyte conditioned medium" (HCM) and measured for malondiadehyde (MDA) content. Then HCM was incubated with primary cultured HSC for 48h, and HSC proliferation, type I collagen gene expression and protein production were observed.


RESULTS
ALT activity and MDA content in the hepatocyte medium were increased remarkably after the cell was injured. HCM could obviously promote HSC proliferation, type I collagen mRNA expression and protein production. SA-A could markedly inhibit ALT activity and MDA content in hepatocytes, and decreased collagen gene expression and protein production.


CONCLUSIONS
The secretion from the peroxidative injured hepatocyte could stimulate HSC activation, SA-A could decrease activation by alleviation of hepatocyte peroxidation.
Hu
Y
Y
Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Wang
R
R
Zhang
X
X
Liu
C
C
Liu
C
C
Liu
P
P
Zhu
D
D
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002109:Caffeic Acids / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007773:Lactates / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D002109:Caffeic Acids; D004365:Drugs, Chinese Herbal; D007773:Lactates; C066201:salvianolic acid A; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase