title: Role of hepatic nitric oxide synthases in rats with thioacetamide-induced acute liver failure and encephalopathy.
abstract: BACKGROUND
  Hepatic encephalopathy is neuropsychiatric derangement secondary to hepatic decompensation or portal-systemic shunting. Nitric oxide (NO) synthase inhibition aggravates encephalopathy and increases mortality in rats with thioacetamide (TAA)-induced acute liver failure, suggesting a protective role of NO. This study investigated the roles of endothelium-derived constitutive NO synthase (eNOS) and inducible NOS (iNOS) in the liver of rats with fulminant hepatic failure and encephalopathy.
  
  
  METHODS
  Male Sprague-Dawley rats (300-350 g) were randomized to receive TAA 350 mg/kg/day, by intraperitoneal injection or normal saline for 3 days. Severity of encephalopathy was assessed with the Opto-Varimex animal activity meter. Plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and bilirubin were measured. Hepatic iNOS and eNOS RNA and protein expressions were assessed by reverse transcription-polymerase chain reaction and Western blot analyses, respectively.
  
  
  RESULTS
  The TAA group showed lower motor activity counts than the normal saline group. Hepatic eNOS, but not iNOS, mRNA and protein expressions were enhanced in the TAA group. In addition, hepatic eNOS mRNA expression was negatively correlated with total movement but positively correlated with ALT and AST. Protein expression of hepatic eNOS was positively correlated with ALT, AST and bilirubin.
  
  
  CONCLUSIONS
  Upregulation of hepatic eNOS was observed in rats with TAA-induced fulminant hepatic failure and encephalopathy, which might play a regulatory role.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, and National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.forename: Sun-Sang
authors.initials: SS
authors.lastname: Wang
authors.forename: Cho-Yu
authors.initials: CY
authors.lastname: Chan
authors.forename: Yi-Chou
authors.initials: YC
authors.lastname: Chen
authors.forename: Fa-Yauh
authors.initials: FY
authors.lastname: Lee
authors.forename: Full-Young
authors.initials: FY
authors.lastname: Chang
authors.forename: Chi-Jen
authors.initials: CJ
authors.lastname: Chu
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
authors.forename: Rei-Hwa
authors.initials: RH
authors.lastname: Lu
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015153:Blotting, Western; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000633:toxicity*
chemical_list: D013853:Thioacetamide; D019001:Nitric Oxide Synthase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin