The effects of thromboxane A2 synthetase inhibitor (OKY-046) on complete hepatic ischemia in rats with obstructive jaundice.
The effects of OKY-046, a thromboxane A2 synthetase inhibitor, on hepatic dysfunction produced by liver cell ischemia were studied in an experimental model of rats with obstructive jaundice. The experiments were performed 7 days after the rats underwent bile duct ligation. Warm total ischemia of the liver was induced by Pringle's method over a 20-min period and the animals were divided into two groups according to whether or not OKY-046 was administered. The reperfusion time was 30 min in each group. OKY-046 was administered via the femoral vein at a rate of 100 micrograms/kg per min from 15 min before the blockade to the end of the experiment. The level of ATP in the liver tissue of the OKY-046 group was elevated slightly, but not significantly, compared to that of the control group. The ratio TXB2/6-keto PGF1 alpha in the liver tissue was lower in the OKY-046 group than in the control group, and significant differences were found between the two groups in the water content of the liver and the mitochondrial score as examined by transmission electron microscopy. Thus, it was observed that an improvement in the balance of TXA2 and PGI2 associated with OKY-046 administration proctected the cellular structure of the mitochondria in the rat liver.
Takahashi
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First Department of Surgery, Yamaguchi University School of Medicine, Ube, Japan.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002779:Cholestasis / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007511:Ischemia / Q000473:pathology*; D008099:Liver / Q000098:blood supply*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D008854:Microscopy, Electron; D008930:Mitochondria, Liver / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D008689:Methacrylates; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D000255:Adenosine Triphosphate; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D013930:Thromboxane-A Synthase; C034364:ozagrel