title: Gabexate mesilate, a synthetic protease inhibitor, attenuates carbon tetrachloride-induced liver injury in rats.
abstract: BACKGROUND
  Gabexate mesilate, a synthetic protease inhibitor, is used to treat acute pancreatitis and disseminated intravascular coagulation because it inhibits various serine proteases; however, whether gabexate mesilate prevents acute liver failure has not yet been studied. The aim of the present study was to investigate the effect of gabexate mesilate in carbon tetrachloride (CCl4)-induced liver injury in rats.
  
  
  METHODS
  Acute hepatic failure was induced by administration of CCl4 intragastrically to male Sprague-Dawley rats. The effects of gabexate mesilate were examined in terms of serum transaminase levels, liver histology, and the prognosis of rats.
  
  
  RESULTS
  Gabexate mesilate treatment significantly decreased the elevation of serum transaminase levels and improved liver histology 24 h after the administration of CCl4 (0.2 ml/100 g rat weight). Plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) decreased significantly in the gabexate mesilate-treated rats compared with saline-treated rats. Gabexate mesilate treatment also significantly improved survival rate after a lethal dose of CCl4 (0.5 ml/100 g rat weight) from 0% to 20%.
  
  
  CONCLUSIONS
  Gabexate mesilate treatment attenuated CCl4-induced liver injury via a suppression of proinflammatory cytokine production. In addition, these investigations suggest that gabexate mesilate treatment may provide therapeutic strategies for human acute liver failure.
authors.affiliation: Department of Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Mikami
authors.forename: Takashi
authors.initials: T
authors.lastname: Goto
authors.forename: Kouichi
authors.initials: K
authors.lastname: Miura
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Ohshima
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yoneyama
authors.forename: Jiun-Guey
authors.initials: JG
authors.lastname: Lin
authors.forename: Daisuke
authors.initials: D
authors.lastname: Watanabe
authors.forename: Daisuke
authors.initials: D
authors.lastname: Segawa
authors.forename: Ei
authors.initials: E
authors.lastname: Kataoka
authors.forename: Tomomi
authors.initials: T
authors.lastname: Shibuya
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D016670:Gabexate / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000097:blood; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000188:drug therapy*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D015842:Serine Proteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016670:Gabexate; D002251:Carbon Tetrachloride; D000637:Transaminases