Tags

Type your tag names separated by a space and hit enter

Selective A2A adenosine agonist ATL-146e attenuates acute lethal liver injury in mice.
J Gastroenterol 2005; 40(5):526-9JG

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.

Authors+Show Affiliations

Department of Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -