Selective A2A adenosine agonist ATL-146e attenuates acute lethal liver injury in mice

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-induce...

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Bibliographic Details
Published in:Journal of gastroenterology 2005-05, Vol.40 (5), p.526-529
Main Authors: Odashima, Masaru, Otaka, Michiro, Jin, Mario, Komatsu, Koga, Wada, Isao, Matsuhashi, Tamotsu, Horikawa, Youhei, Hatakeyama, Natsumi, Oyake, Jinko, Ohba, Reina, Linden, Joel, Watanabe, Sumio
Format: Article
Language:English
Subjects:
Adenosine A2 Receptor Agonists
Animals
Biopsy, Needle
Cyclohexanecarboxylic Acids - pharmacology
Disease Models, Animal
Immunohistochemistry
Liver Failure, Acute - drug therapy
Liver Failure, Acute - pathology
Male
Mice
Mice, Inbred BALB C
Purines - pharmacology
Sensitivity and Specificity
Treatment Outcome
Tumor Necrosis Factor-alpha - drug effects
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Summary: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. 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. 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%. 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.
ISSN:0944-1174
1435-5922
DOI:10.1007/s00535-005-1609-9