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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%.

CONCLUSION

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.

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  • Authors+Show Affiliations

    ,

    Department of Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.

    , , , , , , , , , ,

    Source

    Journal of gastroenterology 40:5 2005 May pg 526-9

    MeSH

    Adenosine A2 Receptor Agonists
    Animals
    Biopsy, Needle
    Cyclohexanecarboxylic Acids
    Disease Models, Animal
    Immunohistochemistry
    Liver Failure, Acute
    Male
    Mice
    Mice, Inbred BALB C
    Purines
    Sensitivity and Specificity
    Treatment Outcome
    Tumor Necrosis Factor-alpha

    Pub Type(s)

    Comparative Study
    Journal Article

    Language

    eng

    PubMed ID

    15942719

    Citation

    Odashima, Masaru, et al. "Selective A2A Adenosine Agonist ATL-146e Attenuates Acute Lethal Liver Injury in Mice." Journal of Gastroenterology, vol. 40, no. 5, 2005, pp. 526-9.
    Odashima M, Otaka M, Jin M, et al. Selective A2A adenosine agonist ATL-146e attenuates acute lethal liver injury in mice. J Gastroenterol. 2005;40(5):526-9.
    Odashima, M., Otaka, M., Jin, M., Komatsu, K., Wada, I., Matsuhashi, T., ... Watanabe, S. (2005). Selective A2A adenosine agonist ATL-146e attenuates acute lethal liver injury in mice. Journal of Gastroenterology, 40(5), pp. 526-9.
    Odashima M, et al. Selective A2A Adenosine Agonist ATL-146e Attenuates Acute Lethal Liver Injury in Mice. J Gastroenterol. 2005;40(5):526-9. PubMed PMID: 15942719.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Selective A2A adenosine agonist ATL-146e attenuates acute lethal liver injury in mice. AU - Odashima,Masaru, AU - Otaka,Michiro, AU - Jin,Mario, AU - Komatsu,Koga, AU - Wada,Isao, AU - Matsuhashi,Tamotsu, AU - Horikawa,Youhei, AU - Hatakeyama,Natsumi, AU - Oyake,Jinko, AU - Ohba,Reina, AU - Linden,Joel, AU - Watanabe,Sumio, PY - 2005/02/24/received PY - 2005/04/01/accepted PY - 2005/6/9/pubmed PY - 2005/10/19/medline PY - 2005/6/9/entrez SP - 526 EP - 9 JF - Journal of gastroenterology JO - J. Gastroenterol. VL - 40 IS - 5 N2 - 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%. CONCLUSION: 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. SN - 0944-1174 UR - https://www.unboundmedicine.com/medline/citation/15942719/Selective_A2A_adenosine_agonist_ATL_146e_attenuates_acute_lethal_liver_injury_in_mice_ L2 - https://dx.doi.org/10.1007/s00535-005-1609-9 DB - PRIME DP - Unbound Medicine ER -