title: Lack of therapeutic effects of gabexate mesilate on the hepatic encephalopathy in rats with acute and chronic hepatic failure.
abstract: OBJECTIVE
  Inflammation plays a pivotal role in liver injury. Gabexate mesilate (GM, a protease inhibitor) inhibits inflammation by blocking various serine proteases. This study examined the effects of GM on hepatic encephalopathy in rats with acute and chronic liver failure.
  
  
  METHODS
  Acute and chronic liver failure (cirrhosis) were induced by intraperitoneal TAA administration (350 mg/kg/day for 3 days) and common bile duct ligation, respectively, in male Sprague-Dawley rats. Rats were randomized to receive either GM (50 mg/10 mL/kg) or saline intraperitoneally for 5 days. Severity of encephalopathy was assessed by the Opto-Varimex animal activity meter and hemodynamic parameters, mean arterial pressure and portal pressure, were measured (only in chronic liver failure rats). Plasma levels of liver biochemistry, ammonia, nitrate/nitrite, interleukins (IL) and tumor necrosis factor (TNF)-alpha were determined.
  
  
  RESULTS
  In rats with acute liver failure, GM treatment significantly decreased the plasma levels of alanine aminotransferase (P = 0.02), but no significant difference of motor activity, plasma levels of ammonia, IL-1beta, IL-6, IL-10 and TNF-alpha or survival was found. In chronic liver failure rats, GM significantly lowered the plasma TNF-alpha levels (P = 0.04). However, there was no significant difference of motor activity, other biochemical tests or survival found. GM-treated chronic liver failure rats had higher portal pressure (P = 0.04) but similar mean arterial pressure in comparison with saline-treated rats.
  
  
  CONCLUSIONS
  Chronic GM treatment does not have a major effect on hepatic encephalopathy in rats with TAA-induced acute liver failure and rats with chronic liver failure induced by common bile duct ligation.
authors.affiliation: Divisions of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chia-Yang
authors.initials: CY
authors.lastname: Hsu
authors.forename: Fa-Yauh
authors.initials: FY
authors.lastname: Lee
authors.forename: Teh-Ia
authors.initials: TI
authors.lastname: Huo
authors.forename: Cho-Yu
authors.initials: CY
authors.lastname: Chan
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.forename: Han-Chih
authors.initials: HC
authors.lastname: Lin
authors.forename: Ching-Chih
authors.initials: CC
authors.lastname: Chang
authors.forename: Tzu-Hua
authors.initials: TH
authors.lastname: Teng
authors.forename: Sun-Sang
authors.initials: SS
authors.lastname: Wang
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D003135:Common Bile Duct / Q000601:surgery; D004195:Disease Models, Animal; D004798:Enzymes / Q000097:blood; D016670:Gabexate / Q000494:pharmacology*; D006501:Hepatic Encephalopathy / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000097:blood; D008026:Ligation; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D017093:Liver Failure / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D017114:Liver Failure, Acute / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017082:Portal Pressure / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D012720:Severity of Illness Index; D013853:Thioacetamide; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D004798:Enzymes; D018836:Inflammation Mediators; D015842:Serine Proteinase Inhibitors; D013853:Thioacetamide; D016670:Gabexate