Protective effect of the thromboxane A2 receptor antagonist ONO 3708 on ischemia-reperfusion injury in the dog liver. 1994

K Hanazaki, and T Kuroda, and Y Haba, and E Shiohara, and S Kajikawa, and F Iida
Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.

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.

UI MeSH Term Description Entries
D008054 Lipid Peroxides Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. Fatty Acid Hydroperoxide,Lipid Peroxide,Lipoperoxide,Fatty Acid Hydroperoxides,Lipid Hydroperoxide,Lipoperoxides,Acid Hydroperoxide, Fatty,Acid Hydroperoxides, Fatty,Hydroperoxide, Fatty Acid,Hydroperoxide, Lipid,Hydroperoxides, Fatty Acid,Peroxide, Lipid,Peroxides, Lipid
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D011169 Portal Vein A short thick vein formed by union of the superior mesenteric vein and the splenic vein. Portal Veins,Vein, Portal,Veins, Portal
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D006503 Hepatic Veins Veins which drain the liver. Hepatic Vein,Vein, Hepatic,Veins, Hepatic
D000596 Amino Acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Amino Acid,Acid, Amino,Acids, Amino
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013928 Thromboxane A2 An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS). Rabbit Aorta Contracting Substance,A2, Thromboxane
D013929 Thromboxane B2 A stable, physiologically active compound formed in vivo from the prostaglandin endoperoxides. It is important in the platelet-release reaction (release of ADP and serotonin). B2, Thromboxane
D015121 6-Ketoprostaglandin F1 alpha The physiologically active and stable hydrolysis product of EPOPROSTENOL. Found in nearly all mammalian tissue. 6-Keto-PGF1 alpha,6-Oxo-PGF1 alpha,6-Oxoprostaglandin F1 alpha,6 Ketoprostaglandin F1 alpha,6 Keto PGF1 alpha,6 Oxo PGF1 alpha,6 Oxoprostaglandin F1 alpha,F1 alpha, 6-Ketoprostaglandin,F1 alpha, 6-Oxoprostaglandin,alpha, 6-Keto-PGF1,alpha, 6-Ketoprostaglandin F1,alpha, 6-Oxo-PGF1,alpha, 6-Oxoprostaglandin F1

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