Raloxifene Ameliorates Liver Fibrosis of Nonalcoholic Steatohepatitis Induced by Choline-Deficient High-Fat Diet in Ovariectomized Mice
| Autor: | Takashi Honda, Teiji Kuzuya, Kazuhiko Hayashi, Yoji Ishizu, Yoshiaki Katano, Fangqiong Luo, Hidemi Goto, Masatoshi Ishigami, Koichi Achiwa, Tetsuya Ishikawa |
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| Rok vydání: | 2014 |
| Předmět: |
Liver Cirrhosis
Selective Estrogen Receptor Modulators medicine.medical_specialty Physiology medicine.drug_class Ovariectomy Gene Expression Mice Fibrosis Non-alcoholic Fatty Liver Disease Internal medicine Nonalcoholic fatty liver disease Hepatic Stellate Cells Medicine Animals Raloxifene RNA Messenger Liver injury business.industry Gastroenterology Estrogen Receptor alpha Alanine Transaminase Organ Size medicine.disease Choline Deficiency Menopause Mice Inbred C57BL Disease Models Animal Endocrinology Liver Estrogen Raloxifene Hydrochloride Ovariectomized rat Female Steatosis business hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Digestive diseases and sciences. 60(9) |
| ISSN: | 1573-2568 |
| Popis: | Background and Aim 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-a, 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-a may play an important role in the beneficial effects of raloxifene on NASH. |
| Databáze: | OpenAIRE |
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