Tetrandrine stimulates the apoptosis of hepatic stellate cells and ameliorates development of fibrosis in a thioacetamide rat model.
OBJECTIVE
To investigate the therapeutic effect of tetrandrine on liver fibrosis induced by thioacetamide in rats in vivo and in vitro.


METHODS
In vitro study: we investigated the effect of tetrandrine on the apoptosis of rat hepatic stellate cells transformed by simian virus 40 (T-HSC/Cl-6), which retains the features of activated cells. In vivo study: hepatic fibrosis was induced in rats by thioacetamide. Tetrandrine was given orally to rats at doses of 5, 10 or 20 mg/kg for 4 wk compared with intraperitoneal injection of interferon-r.


RESULTS
In vitro study: 5, 10 or 25 microg/mL of tetrandrine-induced activation of caspase-3 in t-HSC/Cl-6 cells occurred dose-dependently. In vivo study: tetrandrine treatment as well as interferon-r significantly ameliorated the development of fibrosis as determined by lowered serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil) and the levels of liver hydroxyproline (Hyp), hyaluronic acid (HA), laminin (LN) and also improved histological findings. The effects of tetrandrine at the concentration of 20 mg/kg were better than the other concentration groups.


CONCLUSIONS
Tetrandrine promotes the apoptosis of activated HSCs in vitro. Tetrandrine administration can prevent liver fibrosis and liver damage induced by thioacetamide in rats in vivo, indicating that it might exert a direct effect on rat HSCs.
Yin
Ming-Fu
MF
Key Laboratory of Organism Functional Factors of the Changbai Mountain (Yanbian University), Ministry of Education and College of Pharmacy, Yanbian University, Yanji 133002, Jilin Province, China.
Lian
Li-Hua
LH
Piao
Dong-Ming
DM
Nan
Ji-Xing
JX
D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D053148:Caspase 3 / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide / Q000494:pharmacology
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D013853:Thioacetamide; C009438:tetrandrine; D053148:Caspase 3; D006909:Hydroxyproline