Effects of dietary supplementation with vitamin E and selenium on rat hepatic stellate cell apoptosis.
OBJECTIVE
To evaluate the effects of dietary supplementation with vitamin E and selenium on proliferation and apoptosis of hepatic stellate cells (HSCs), in acute liver injury induced by CCl(4), and to explore their role in the recovery from hepatic fibrosis phase.


METHODS
An acute liver damage model of rats was established by intraperitoneal injection of carbon tetrachloride (0.3 mL/100 g body weight) twice a week, then the rats were killed at 6, 24, 48, and 72 h after the first and third injection, respectively. A liver fibrosis model was established by the same injection for 8 wk. Then three rats were killed at 3, 7, 14, and 28 d after the last injection, respectively. The rats from the intervention group were fed with chow supplemented with vitamin E (250 mg/kg) and selenium (0.2 mg/kg), and the rats in the normal control group and pathological group were given standard chow. Livers were harvested and stained with hematoxylin and eosin, Sirius red. Activated HSCs were determined by alpha-smooth muscle actin immunohistochemistry staining. Apoptotic HSCs were determined by dual staining with the terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL) and alpha-smooth muscle actin immunohistochemistry. Serum alanine aminotransferase and aspartate aminotransferase were also analyzed.


RESULTS
In the acute liver damage model, the degree of liver injury was more serious in the pathological group than in the intervention group. At each time point, the number of activated HSCs was less in the intervention group than in the pathological group, while the number of apoptotic HSCs was more in the intervention group than in the pathological group. In the liver fibrosis model, the degree of liver fibrosis was more serious in the pathological group than in the intervention group. At each time point, the number of activated HSCs was less in the intervention group than in the pathological group, and the number of apoptotic HSCs was more in the intervention group than in the pathological group.


CONCLUSIONS
Vitamin E and selenium supplementation at the given level can inhibit CCl(4)-induced activation and proliferation of HSCs and promote the apoptosis of activated HSCs in acute damage phase. Vitamin E and selenium can also effectively decrease the degree of hepatic fibrosis and promote the recovery process.
Shen
Xiu-Hua
XH
Department of Nutrition, Shanghai Second Medical University, Shanghai 200025, China. srachel@sina.com
Cheng
Wu-Feng
WF
Li
Xuan-Hai
XH
Sun
Jian-Qin
JQ
Li
Feng
F
Ma
Ling
L
Xie
Liang-Min
LM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019587:Dietary Supplements; D004359:Drug Therapy, Combination; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012643:Selenium / Q000494:pharmacology*; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D014810:Vitamin E; D002251:Carbon Tetrachloride; D012643:Selenium