Rhein inhibits liver fibrosis induced by carbon tetrachloride in rats.
OBJECTIVE
To investigate the effect of rhein on liver fibrosis induced by the exposure of carbon tetrachloride (CCl4)/ethanol in rats.


METHODS
Male Wistar rats were divided into four study groups (n=10 each group): healthy controls, CCl4/ethanol-injured rats left untreated, and CCl4/ethanol-injured rats treated with rhein of low-dose (25 mg/kg) and high-dose (100 mg/kg). Rhein was given once a day since rat received CCl4/ethanol injury. After administration of rhein for 6 weeks rats were killed. The following parameters were determined: the activity of alanine aminotransferase (ALT), hyalauronic acid (HA) and procollagen type III (PC-III) concentrations in serum, liver malondialdehyde (MDA) level, the degree of liver fibrosis, and the expression of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta1 (TGF-beta1) in liver tissue.


RESULTS
The treatment of rhein markedly reduced the ALT activity, HA and PC-III concentrations, and liver MDA level in CCl4/ethanol-injured rats (P<0.01). It also improved significantly histological changes of fibrosis and decreased the expression of alpha-SMA and TGF-beta1 in liver of these rats (P<0.05 or P<0.01).


CONCLUSIONS
Rhein has protective effect on liver injury and can inhibit liver fibrosis induced by CCl4/ethanol in rats. The mechanisms possibly contribute to its action of antioxidant and anti-inflammatory activity, also associated with its effect of inhibiting TGF-beta1 and suppressing the activation of hepatic stellate cells.
Guo
Mei-Zi
MZ
Department of Gastroenterology, Second Affiliated Hospital, Chongqing 400010, China. aguoyier@sina.com.cn
Li
Xiao-Sheng
XS
Xu
Hai-Rong
HR
Mei
Zhe-Chuan
ZC
Shen
Wei
W
Ye
Xiu-Feng
XF
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002252:Carbon Tetrachloride Poisoning; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000494:pharmacology*; D011347:Procollagen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000880:Anthraquinones; D000975:Antioxidants; D011347:Procollagen; D016212:Transforming Growth Factor beta; D006899:Mixed Function Oxygenases; C020491:rhein