[Effects of genistein on the fenestrae, proliferation and nitric oxide synthesis of liver sinusoidal endothelial cells from carbon tetrachloride-induced experimental hepatic fibrosis rats].
OBJECTIVE
To investigate the effects of genistein, a tyrosine protein kinase inhibitor, on the fenestrae, proliferation and nitric oxide (NO) synthesis of the liver sinusoidal endothelial cells from CCl(4)-induced hepatic fibrosis rats in vitro.


METHODS
By in situ collagenase perfusion and two-step percoll gradient centrifugation, SECs were isolated and cultured from normal and CCl(4)-treated Wistar rats. The fenestrae of SECs were observed by the scanning electron microscopy, and the SECs cell proliferation was determined by the MTT assay. The concentrations of NO in the cultured medium of SECs were detected indirectly by measurement of nitrates and nitrites (the stable products of NO) using the nitrate reduction method.


RESULTS
Scanning electron microscopic studies revealed that the number of fenestrae in SECs from all stage of hepatic fibrotic rats was decreased markedly as compared with the SECs from normal controls; however, no obvious changes in the fenestrae of SECs were observed after treated with genistein (100 mumol/L) for 24 hours. After treated with 100 mumol/L genistein for 24 hours, the cell proliferation rates of SECs from all stages of hepatic fibrosis were decreased significantly was compared with the control group (P<0.05). The synthesis of NO by SECs from all stages of hepatic fibrosis was markedly lower than those of normal controls. Treatment with 100 mumol/L genistein for 24 hours could increase the synthesis of NO by SECs from the early stage (stage I) of fibrosis; however, this effect of genistein was not observed in SECs from stage II or III of fibrosis at this concentration.


CONCLUSIONS
The results suggest that genistein may play an important role in regulating the function of SECs.
Lab of Department of Internal Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Xiaojing
X
Liu
Minghui
M
Huang
Niang
N
Cheng
Wenjun
W
Xiao
Yiping
Y
Wang
D000818:Animals; D002251:Carbon Tetrachloride; D002455:Cell Division / Q000187:drug effects; D004727:Endothelium / Q000187:drug effects* / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D006131:Growth Inhibitors; D009569:Nitric Oxide; D002251:Carbon Tetrachloride; D019833:Genistein