Up-regulated thromboxane production in the rat liver with biliary obstruction does not contribute to promote hepatic injury.
This study sought to determine whether in vivo inhibition of thromboxane A2 (TXA2) action contribute to attenuate hepatic damage after bile duct ligation (BDL). Male Wistar rats were assigned to sham operation or BDL. At the time of operation, infusion pump with saline, ozagrel natrium (TXA2 synthase inhibitor), or SQ29548 (TXA2 receptor antagonists) was implanted in the abdominal cavity. Plasma alanine aminotransferase, aspartate aminotransferase, hyaluronic acid, and total bilirubin levels were measured at 4 days after the operation. The levels of plasma TXB2, a stable metabolite of TXA2, were significantly increased after BDL. Gene expression of TXA2 synthase was also significantly upregulated in the liver. Nonetheless, either an inhibition of TXA2 synthesis by ozagrel natrium or a blockade of TXA2 receptor by SQ29548 has no effect in every measured parameter related to hepatic function. These results indicated that despite a highly increased production in the liver, TXA2 is not directly related to the hepatic injury in BDL rats.
Yokoyama
Yukihiro
Y
Department of Surgery, Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. yyoko@med.nagoya-u.ac.jp
Kawai
Toru
T
Kawai
Satoru
S
Kitagawa
Tomomi
T
Watanabe
Katsutaka
K
Kawai
Kiyotaka
K
Nagino
Masato
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001663:Bilirubin / Q000097:blood; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006820:Hyaluronic Acid / Q000097:blood; D006834:Hydrazines / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology* / Q000293:injuries / Q000473:pathology; D008107:Liver Diseases / Q000097:blood*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000097:blood* / Q000494:pharmacology; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000096:biosynthesis; D013997:Time Factors
D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D008689:Methacrylates; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013929:Thromboxane B2; D013928:Thromboxane A2; C045749:SQ 29548; D006820:Hyaluronic Acid; D000410:Alanine Transaminase; D013930:Thromboxane-A Synthase; C034364:ozagrel; D001663:Bilirubin