title: Selective A2A adenosine agonist ATL-146e attenuates acute lethal liver injury in mice.
abstract: BACKGROUND
  D-Galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury is an experimental model of fulminant hepatic failure in which tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role. We examined the effects of a highly selective adenosine A2A receptor agonist (ATL-146e) on GalN/LPS-induced fulminant hepatic failure.
  
  
  METHODS
  Mice were given an intraperitoneal dose of GalN (800 mg/g body weight)/LPS (100 ng/g body weight) with and without ATL-146e (0.01 microg/kg) treatment. Liver injury was assessed biochemically and histologically. Also, TNF-alpha levels in the serum were determined.
  
  
  RESULTS
  The serum liver enzyme (ALT) level in vehicle-treated mice was 20 960 +/- 2800 IU/ml and was reduced by 63% to 7800 +/- 1670 IU/ml by treatment with 0.01 microg/kg per minute ATL146e, P < 0.05. Treatment with ATL-146e significantly reduced serum TNF-alpha and greatly reduced inflammation assessed by histopathologic examination compared with control mice treated with GalN/LPS. ATL-146e also reduced lethality at 12 h from 65% to 13%.
  
  
  CONCLUSIONS
  The present findings suggest that the highly selective adenosine A2A receptor agonist (ATL-146e) prevents endotoxin-induced lethal liver injury by suppression of TNF-alpha secretion.
authors.affiliation: Department of Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Odashima
authors.forename: Michiro
authors.initials: M
authors.lastname: Otaka
authors.forename: Mario
authors.initials: M
authors.lastname: Jin
authors.forename: Koga
authors.initials: K
authors.lastname: Komatsu
authors.forename: Isao
authors.initials: I
authors.lastname: Wada
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Matsuhashi
authors.forename: Youhei
authors.initials: Y
authors.lastname: Horikawa
authors.forename: Natsumi
authors.initials: N
authors.lastname: Hatakeyama
authors.forename: Jinko
authors.initials: J
authors.lastname: Oyake
authors.forename: Reina
authors.initials: R
authors.lastname: Ohba
authors.forename: Joel
authors.initials: J
authors.lastname: Linden
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D001707:Biopsy, Needle; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D017114:Liver Failure, Acute / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011687:Purines / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects*
chemical_list: C431129:ATL 146e; D058908:Adenosine A2 Receptor Agonists; D003509:Cyclohexanecarboxylic Acids; D011687:Purines; D014409:Tumor Necrosis Factor-alpha