title: Therapeutic effects of vitamin A on experimental cholestatic rats with hepatic fibrosis.
abstract: OBJECTIVE
  The aim of this study is to investigate the role of hepatic stellate cells (HSCs) and the effect of vitamin A administration on liver damage induced by bile duct ligation (BDL) and administration of CCl(4).
  
  
  METHODS
  Two types of animal model were used; one was BDL as a model of biliary atresia, the other was CCl(4)-induced hepatic fibrosis. Pathological changes of the liver with or without administration of vitamin A were compared by light and electron microscopy with focusing on HSCs in each experimental group. Immunohistochemical examination was performed with anti-keratinocyte growth factor (KGF), anti-alpha-smooth muscle actin (α-SMA), and anti-glial fibrillary acidic protein (GFAP) antibodies, as markers of fibrosis.
  
  
  RESULTS
  On light microscopic findings, periportal inflammation with bile ductular proliferation was obvious in BDL group and pericentral necrosis with fatty degeneration was observed in CCl(4) group, both of which were ameliorated by subcutaneous injection of vitamin A. Electron microscopy showed lipid droplets were almost depleted in the HSCs treated with BDL or CCl(4), which improved with vitamin A administration. Immunohistochemistry demonstrated that enhanced expression of all three fibrotic markers in the BDL group was diminished by vitamin A administration.
  
  
  CONCLUSIONS
  Although most of our data are qualitative observation, vitamin A may ameliorate hepatic fibrosis in the BDL model by restoring vitamin A in the HSCs.
authors.affiliation: Department of Pediatric Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan. mkenwood@po.synapse.ne.jp
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Murakami
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Kaji
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Shimono
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayashida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsufuji
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Tsuyama
authors.forename: Rie
authors.initials: R
authors.lastname: Maezono
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Kosai
authors.forename: Hideo
authors.initials: H
authors.lastname: Takamatsu
mesh_terms: D000199:Actins / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000032:analysis; D002779:Cholestasis / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D051523:Fibroblast Growth Factor 7 / Q000276:immunology; D005500:Follow-Up Studies; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000648:ultrastructure; D008106:Liver Cirrhosis, Experimental / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014801:Vitamin A / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D000199:Actins; D000906:Antibodies; D051523:Fibroblast Growth Factor 7; D005904:Glial Fibrillary Acidic Protein; D014801:Vitamin A; D014815:Vitamins; C498862:Acta2 protein, rat