PMID- 10629874
OWN - NLM
STAT- MEDLINE
DCOM- 20000216
LR  - 20190831
IS  - 0015-5691 (Print)
IS  - 0015-5691 (Linking)
VI  - 114 Suppl 1
DP  - 1999 Oct
TI  - [Adenosine reduces ischemia/reperfusion-induced liver injury by inhibiting 
      leukocyte activation].
PG  - 159P-167P
AB  - To examine whether adenosine reduces ischemia/reperfusion (I/R)-induced liver 
      injury by inhibiting leukocyte activation via A2 receptor (A2R), we investigated 
      the effects of adenosine and YT-146, selective A2A receptor (A2AR) agonist, on 
      I/R-induced liver injury in rats. Adenosine and YT-146, in the range of 
      concentrations of 10(-7)-10(-5) M, significantly inhibited the 
      formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophil elastase release 
      from isolated neutrophils by about 35% in vitro. Adenosine and YT-146, in the 
      range of concentrations of 10(-7)-10(-5) M, significantly inhibited the 
      endotoxin-stimulated TNF-alpha production by monocytes to less than 50% of the 
      control. Although ZM241385, a selective A2AR antagonist, significantly enhanced 
      the fMLP-induced neutrophil elastase release in isolated neutrophils in vitro, 
      this agent did not affect the endotoxin-stimulated TNF-alpha production by 
      monocytes. Male Wistar rats were subjected to complete ischemia of median and 
      left lobes of liver for 60 min and the subsequent reperfusion. Serum levels of 
      transaminases increased over time after hepatic I/R, peaking at 12 hrs after 
      reperfusion. Intravenous infusion of Adenosine (1 and 10 mg/kg/hr) and YT-146 
      (0.1 and 1 mg/kg/hr) significantly inhibited the I/R-induced increases in serum 
      transaminase levels 12 hrs after reperfusion. The I/R-induced decrease in hepatic 
      tissue blood flow was significantly inhibited by adenosine and YT-146. Hepatic 
      levels of TNF-alpha, cytokine-induced neutrophil chemoattractant (a member of 
      interleukin-8), and myeloperoxidase were significantly increased after I/R. These 
      increases were significantly inhibited by administration of adenosine and YT-146. 
      However, ZM241385 did not reduce the I/R-induced liver injury and it inhibited 
      neither the decrease in hepatic tissue blood flow, nor the indicators of 
      leukocyte activation. These findings suggest that adenosine may reduce 
      I/R-induced liver injury mainly by inhibiting hepatic TNF-alpha production via 
      A2AR, thereby reducing neutrophil activation.
FAU - Harada, N
AU  - Harada N
AD  - Department of Pharmacology, School of Medicine, Fukuoka University.
FAU - Okajima, K
AU  - Okajima K
FAU - Katsuragi, T
AU  - Katsuragi T
LA  - jpn
PT  - Journal Article
PL  - Japan
TA  - Nihon Yakurigaku Zasshi
JT  - Nihon yakurigaku zasshi. Folia pharmacologica Japonica
JID - 0420550
RN  - 0 (Alkynes)
RN  - 0 (Receptors, Purinergic P1)
RN  - 0 (Triazines)
RN  - 0 (Triazoles)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (ZM 241385)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 90596-75-1 (YT 146)
RN  - EC 2.6.1.- (Transaminases)
RN  - EC 3.4.21.37 (Leukocyte Elastase)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/analogs & derivatives/*pharmacology
MH  - Alkynes/pharmacology
MH  - Animals
MH  - Humans
MH  - In Vitro Techniques
MH  - Leukocyte Elastase/metabolism
MH  - Liver/*blood supply
MH  - Male
MH  - Monocytes/metabolism
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophil Activation/*drug effects
MH  - Neutrophils/enzymology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Purinergic P1/drug effects
MH  - Reperfusion Injury/*prevention & control
MH  - Transaminases/blood
MH  - Triazines/pharmacology
MH  - Triazoles/pharmacology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2000/01/12 09:00
MHDA- 2000/02/19 09:00
CRDT- 2000/01/12 09:00
PHST- 2000/01/12 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 2000/01/12 09:00 [entrez]
AID - 10.1254/fpj.114.supplement_159 [doi]
PST - ppublish
SO  - Nihon Yakurigaku Zasshi. 1999 Oct;114 Suppl 1:159P-167P. doi: 
      10.1254/fpj.114.supplement_159.