title: Pravastatin for thioacetamide-induced hepatic failure and encephalopathy.
abstract: BACKGROUND
  Nitric oxide (NO) inhibition aggravates hepatic damage and encephalopathy and increases mortality in rats with thioacetamide (TAA)-induced acute liver failure. Statins enhance NO production but whether they influence the above parameters are unknown.
  
  
  METHODS
  Male Sprague-Dawley rats were used. In the first series, TAA (350 mg/kg per day, i.p. for 3 days) was administered to induce acute liver failure. Control rats received saline. Rats received distilled water or pravastatin (20 mg/kg per day, p.o.) from 2 days before to 3 days after TAA or saline injection. In the second series, liver cirrhosis was induced by common bile duct ligation (BDL). Sham-operated rats served as controls. Rats received distilled water or pravastatin for 5 or 14 days until the 42nd day after operation. On the last day of treatment, survival, motor activities, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, ammonia and brain histology were evaluated.
  
  
  RESULTS
  Thioacetamide and BDL rats showed higher ALT, AST, bilirubin and ammonia levels and lower motor activity counts compared with their corresponding control groups. In TAA rats, pravastatin elicited higher total and ambulatory motor activity counts and lower AST and total bilirubin levels. Survival was improved, whereas brain H&E staining was not significantly different in TAA rats with or without pravastatin treatment. In BDL groups, rats with or without pravastatin treatment were not different in motor activity counts and liver biochemistry.
  
  
  CONCLUSIONS
  Pravastatin ameliorates hepatic encephalopathy and liver biochemistry and improves survival in rats with acute liver failure, but not in those with cirrhosis.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.forename: Ching-Chih
authors.initials: CC
authors.lastname: Chang
authors.forename: Sun-Sang
authors.initials: SS
authors.lastname: Wang
authors.forename: Cho-Yu
authors.initials: CY
authors.lastname: Chan
authors.forename: Fa-Yauh
authors.initials: FY
authors.lastname: Lee
authors.forename: Chiao-Lin
authors.initials: CL
authors.lastname: Chuang
authors.forename: I-Fan
authors.initials: IF
authors.lastname: Hsin
authors.forename: Tzu-Hua
authors.initials: TH
authors.lastname: Teng
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D004195:Disease Models, Animal; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000188:drug therapy*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017035:Pravastatin / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000633:toxicity
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013853:Thioacetamide; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D017035:Pravastatin