Protective effect of the thromboxane A2 receptor antagonist ONO 3708 on ischemia-reperfusion injury in the dog liver.
BACKGROUND
Prostaglandins are widely known to have cytoprotective effects in a variety of conditions. Thromboxane A2 has the opposite effect of prostaglandins. In this study the effects of the thromboxane A2 receptor antagonist ONO 3708 on ischemia and subsequent reperfusion in the dog liver was evaluated.


METHODS
Mongrel dogs weighing from 10 to 15 kg were divided into three groups: a control group, a group with induced liver ischemia and subsequent reperfusion, and a group that received ONO 3708 and then underwent induced liver ischemia and subsequent reperfusion. Liver ischemia was induced by the Pringle procedure for 60 minutes. The concentrations of total free amino acids, aromatic amino acids, and branched-chain amino acids in blood taken from the portal and hepatic veins were examined before and after the Pringle procedure in the latter two groups and at the corresponding points in the control group.


RESULTS
Disturbances in amino acid metabolism in the liver occurred 5 minutes after the declamping in the ischemic group, and prostaglandin I2 and thromboxane A2 levels and lipid peroxide production, were increased. In contrast, hepatic amino acid metabolism was unchanged, and prostaglandin I2 and thromboxane A2, and lipid peroxide production, were normalized in the group that was treated with ONO 3708.


CONCLUSIONS
ONO 3708 appears to protects hepatic tissue from ischemia-reperfusion injury through free-radical scavenging, by increasing prostaglandin I2 levels, and by decreasing thromboxane A2 production.
Hanazaki
K
K
Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
Kuroda
T
T
Haba
Y
Y
Shiohara
E
E
Kajikawa
S
S
Iida
F
F
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000596:Amino Acids / Q000097:blood / Q000378:metabolism; D000818:Animals; D004285:Dogs; D006503:Hepatic Veins; D008054:Lipid Peroxides / Q000097:blood; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D011169:Portal Vein; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood
D000596:Amino Acids; D008054:Lipid Peroxides; D017482:Receptors, Thromboxane; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C049855:ONO 3708