Modulation of arachidonic acid metabolism in endotoxic horses: comparison of flunixin meglumine, phenylbutazone, and a selective thromboxane synthetase inhibitor.
Two cyclooxygenase inhibitors (flunixin meglumine and phenylbutazone) and a selective thromboxane synthetase inhibitor were assessed in the management of experimental equine endotoxemia. Drugs or saline solution were administered to 16 horses 15 minutes before administration of a sublethal dose of endotoxin (Escherichia coli 055:B5). Plasma concentrations of thromboxane B2 (TxB2), prostacyclin (6-keto PGF1 alpha), plasma lactate, and hematologic values and clinical appearance were monitored for 3 hours after endotoxin administration. Pretreatment with flunixin meglumine (1 mg/kg of body weight) prevented most of the endotoxin-induced changes and correlated with a significant decrease in plasma TxB2 and 6-keto PGF1 alpha concentrations, compared with concentrations in nontreated horses (ie, pretreated with saline solution). Pretreatment with phenylbutazone (2 mg/kg) attenuated the effects of endotoxin and was associated with a brief, early, significant increase in plasma TxB2 concentrations, but not in plasma 6-keto PGF1 alpha concentrations. Pretreatment with the thromboxane synthetase inhibitor did not appear to clinically benefit the horses involved; however, arachidonic acid metabolism was redirected to prostacyclin production.
Moore
J N
JN
Hardee
M M
MM
Hardee
G E
GE
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D003002:Clonixin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004731:Endotoxins / Q000008:administration & dosage / Q000097:blood*; D004926:Escherichia coli; D006736:Horses; D007093:Imidazoles / Q000494:pharmacology*; D007773:Lactates / Q000097:blood; D008297:Male; D009539:Nicotinic Acids / Q000494:pharmacology*; D010653:Phenylbutazone / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D001095:Arachidonic Acids; D004731:Endotoxins; D007093:Imidazoles; D007773:Lactates; D009539:Nicotinic Acids; D016718:Arachidonic Acid; C039242:dazmegrel; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C014558:flunixin meglumine; D013930:Thromboxane-A Synthase; D010653:Phenylbutazone; D003002:Clonixin