Post-ischemic intraportal adenosine administration protects against reperfusion injury of canine liver.
Although adenosine has been postulated to inhibit ischemia-reperfusion injury in various tissues, its in vivo cytoprotective mechanism is not fully known. The aim of this study was to determine the effect of intraportally infused adenosine on reperfusion injury in the canine liver. Two h ischemia and reperfusion of the liver were induced in beagle dogs by clamping the portal triad. Either adenosine or saline was infused in the portal vein after reperfusion for 60 min. Levels of serum aspartate aminotransferase and alanine aminotransferase and the survival of animals were examined. Hepatic levels of protein carbonyls and glutathione were also measured, as markers of oxidative stress. One h after reperfusion, the liver was perfused with nitroblue tetrazolium and the formation of formazan was observed to evaluate superoxide formation. Twenty-four h after reperfusion, 100% of animals in the adenosine group and 33% of animals in the control group survived. Adenosine significantly decreased the reperfusion-induced increase in serum levels of aspartate aminotransferase and alanine aminotransferase. Adenosine also suppressed the formation of protein carbonyls and the decrease in glutathione levels. Histologically, neutrophil infiltration, superoxide formation, and apoptosis were decreased by adenosine. These results suggest that intraportally infused adenosine attenuates reperfusion injury of the liver, presumably by suppressing the activation of neutrophils and oxidative stress.
Sakata
C
C
Second Department of Surgery, Osaka City University Medical School, 1-4-3, Asahimachi, Abeno, Osaka 545-8585, Japan.
Tanaka
H
H
Takemura
S
S
Hirohashi
K
K
Minamiyama
Y
Y
Nakamura
A
A
Inoue
M
M
Kinoshita
H
H
D000241:Adenosine / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D017209:Apoptosis; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005609:Free Radicals / Q000032:analysis; D006503:Hepatic Veins; D007262:Infusions, Intravenous; D008099:Liver / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011336:Probability; D012016:Reference Values; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000517:prevention & control; D015996:Survival Rate; D014665:Vasodilator Agents / Q000494:pharmacology*
D005609:Free Radicals; D014665:Vasodilator Agents; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000241:Adenosine