title: Raloxifene Ameliorates Liver Fibrosis of Nonalcoholic Steatohepatitis Induced by Choline-Deficient High-Fat Diet in Ovariectomized Mice.
abstract: OBJECTIVE
  The prevalence of nonalcoholic fatty liver disease (NAFLD) is higher in men than in women, but according to some epidemiological studies, this gender difference disappears after menopause. Estrogen therapy protects against NAFLD and nonalcoholic steatohepatitis (NASH) after menopause. We investigated the therapeutic effect of raloxifene, a second-generation selective estrogen-receptor modulator, on NASH induced by a choline-deficient high-fat (CDHF) diet in female ovariectomized (OVX) mice.
  
  
  METHODS
  Seven-week-old female C57BL/6J mice were divided into three experimental groups as follows: (1) sham operation (SHAM group), (2) ovariectomy (OVX group), and (3) ovariectomy + raloxifene (intraperitoneal injection, 3 mg/kg body weight/day; OVX + RLX group). These three groups of mice were fed a CDHF diet for 8 weeks; choline-sufficient high-fat (CSHF) diet was used as control diet. Serum biochemical indicators of hepatic function and liver histological changes were evaluated.
  
  
  RESULTS
  Compared with CSHF diet, ovariectomy enhances liver injury and fibrosis in CDHF diet-fed mice. Serum alanine aminotransferase (ALT) levels were significantly lower in the OVX + RLX group than in the OVX group. The OVX group developed extensive steatosis with inflammation and fibrosis. Lobular inflammatory scores and fibrosis staging in the OVX + RLX group were significantly lower than in the OVX group. Furthermore, the OVX + RLX group exhibited significantly higher expression of hepatic estrogen receptor-α, which was significantly lower in the OVX group than in the SHAM group.
  
  
  CONCLUSIONS
  Raloxifene may ameliorate progression of liver fibrosis of NASH induced by CDHF diet in ovariectomized female mice, and up-regulation of estrogen receptor-α may play an important role in the beneficial effects of raloxifene on NASH.
authors: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan, luo_fangqiong@hotmail.com.
authors: Fangqiong
authors: F
authors: Luo
authors: Masatoshi
authors: M
authors: Ishigami
authors: Koichi
authors: K
authors: Achiwa
authors: Yoji
authors: Y
authors: Ishizu
authors: Teiji
authors: T
authors: Kuzuya
authors: Takashi
authors: T
authors: Honda
authors: Kazuhiko
authors: K
authors: Hayashi
authors: Tetsuya
authors: T
authors: Ishikawa
authors: Yoshiaki
authors: Y
authors: Katano
authors: Hidemi
authors: H
authors: Goto
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D002796:Choline Deficiency; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D055166:Hepatic Stellate Cells; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications* / Q000188:drug therapy; D009929:Organ Size; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*
chemical_list: D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D000410:Alanine Transaminase