Topic:Cyclooxygenase
Cyclooxygenase (COX) is an enzyme that plays a significant role in the inflammatory process in horses. It is responsible for the conversion of arachidonic acid into prostaglandins, which are lipid compounds that mediate inflammation and pain. There are two main isoforms of cyclooxygenase: COX-1, which is involved in maintaining normal physiological functions such as gastric mucosal protection and platelet aggregation, and COX-2, which is primarily induced during inflammatory responses. Understanding the expression and regulation of cyclooxygenase in horses is important for the development of anti-inflammatory treatments, such as non-steroidal anti-inflammatory drugs (NSAIDs), that target these pathways. This page collates peer-reviewed research and scholarly articles that explore the function, regulation, and therapeutic implications of cyclooxygenase in equine health and disease.
Effects of anti-arthritis preparations on gene expression and enzyme activity of cyclooxygenase-2 in cultured equine chondrocytes. To determine the effects of recombinant equine interleukin -1beta (reIL-1beta) and 4 anti-inflammatory compounds on the expression and activity of cyclooxygenase (COX)-2 in cultured equine chondrocytes. Methods: Articular cartilage from 9 young adult horses. Methods: Reverse transcriptase-polymerase chain reaction methods were used to amplify a portion of equine COX-2 to prepare a cDNA probe. Northern blot analysis was used to quantify the expression of COX-2 in first-passage cultures of equine articular chondrocytes propagated in media containing dexamethasone (DEX), phenylbutazone (PBZ), pol...
In vitro effects of cyclooxygenase inhibitors in whole blood of horses, dogs, and cats. To determine potency and selectivity of nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase- (COX-) specific inhibitors in whole blood from horses, dogs, and cats. Methods: Blood samples from 30 healthy horses, 48 healthy dogs, and 9 healthy cats. Methods: Activities of COX-1 and COX-2 were determined by measuring coagulation-induced thromboxane and lipopolysaccharide-induced prostaglandin E2 concentrations, respectively, in whole blood with and without the addition of various concentrations of phenylbutazone, flunixin meglumine, ketoprofen, diclofenac, indomethacin, meloxicam, car...
The role of cyclooxygenase inhibitors in repair of ischaemic-injured jejunal mucosa in the horse. Cyclooxygenase inhibitors are administered to horses to prevent endotoxin-induced elaboration of prostaglandins. However, PGE2 and PGI2 stimulate repair of injured intestine. There are 2 isoforms of cyclooxygenase: COX-1, which constitutively produces prostaglandins and COX-2, which is induced by inflammation. We hypothesised that the nonspecific cyclooxygenase inhibitor flunixin meglumine would retard repair of ischaemic intestinal injury by preventing production of reparative prostaglandins, whereas the selective COX-2 inhibitor, etodolac, would permit repair as a result of continued COX-1 p...
Pharmacokinetics and pharmacodynamics of ketoprofen enantiomers in the horse. Pharmacokinetic and pharmacodynamic parameters were established for enantiomers of the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (KTP), each administered separately at a dose level of 1.1 mg/kg to a group of six New Forest geldings, in a three-period cross-over study using a tissue cage model of inflammation. For both S(+)-and R(-)-KTP, penetration into tissue cage fluid (transudate) and inflamed tissue cage fluid (exudate) was rapid, and clearances from exudate and transudate were much slower than from plasma. AUC values were, therefore, higher for exudate and, to a lesser degre...
PGE2 inhibits acetylcholine release from cholinergic nerves in canine but not equine airways. The effects of exogenous prostaglandin E2 (PGE2) and endogenous prostanoids on cholinergic neurotransmission were determined by measurement of acetylcholine (ACh) release from canine and equine airway tissues. Trachealis strips and bronchial segments were suspended in 2 ml tissue baths. ACh release was induced by electrical field stimulation (EFS), and its content in tissue bath liquid was measured by high pressure liquid chromatography (HPLC) with electrochemical detection. In canine airways, exogenous PGE2 (10(-9) to 10(-7) M) inhibited ACh release concentration-dependently, whereas inhibiti...
Comparison of the effects of ketoprofen and flunixin meglumine on the in vitro response of equine peripheral blood monocytes to bacterial endotoxin. The purpose of this study was to investigate the in vitro effects of flunixin meglumine, a cyclo-oxygenase inhibitor, and ketoprofen, a reported cyclo-oxygenase and lipoxygenase inhibitor, on the synthesis of cyclo-oxygenase end-products thromboxane B2 and prostaglandin E2, lipoxygenase derived 12-hydroxyeicosatetraenoic acid, tumor necrosis factor and tissue factor. Six adult horses were each randomly administered flunixin meglumine (1.1 mg/kg) or ketoprofen (2.2 mg/kg) intravenously every 12 hours with the drug treatments separated by two weeks. Blood samples were obtained prior to initiatin...
Influence of cyclooxygenase inhibitors on furosemide-induced hemodynamic effects during exercise in horses. Furosemide, which commonly is used as a prophylactic treatment for exercise-induced pulmonary hemorrhage in horses, may mediate hemodynamic changes during exercise by altering prostaglandin metabolism. To determine if furosemide's hemodynamic effects during exercise in horses could be reversed, cyclooxygenase inhibitors were administered with furosemide. Four treatments were administered 4 hours prior to treadmill exercise at 9 and 13 m/s. They included a control treatment (10 ml of 0.9% NaCl solution, IV), furosemide (1 mg/kg of body weight, IV) administered alone, and furosemide in combinati...
Incidence, diagnosis and treatment of postoperative complications in colic cases. A survey of 259 surgical colic cases revealed that over 50 per cent of fatalities occurred in the postoperative period. Postoperative ileus and circulatory/endotoxaemic shock accounted for 70 per cent of these deaths. Other less important complications were salmonellosis, long bone fracture, adhesions, haemorrhage, laminitis, wound infection and ischaemic muscle damage. Close monitoring of postoperative progress is necessary to enable early diagnosis and treatment. Recent developments in understanding of the pathophysiology of endotoxic shock and ileus may lead to more successful treatment reg...
Effects of flunixin meglumine on cardiopulmonary responses to endotoxin in ponies. The effects of endotoxemia on cardiopulmonary parameters, before and after cyclooxygenase blockade, were determined in anesthetized ponies spontaneously breathing a mixture of halothane and 100% O2. Escherichia coli endotoxin was infused intravenously at 20 micrograms/kg for 1 h followed by 10 micrograms X kg-1 X h-1 the subsequent 4 h. By 15 min endotoxin increased mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), and alveolar dead space ventilation (VDA/VT), and these were followed by a return to base-line values by 30 min. A second increase in PVR occurred by 5 h ...
Endotoxin-induced eicosanoid production by equine vascular endothelial cells and neutrophils. Dispersed equine vascular endothelial cells grown in tissue culture, and freshly isolated neutrophils were used to determine direct effects of endotoxin on cyclooxygenase and lipoxygenase products. Endothelial cells (10(7)/ml) or neutrophils (2 X 10(6)/ml) were incubated with (a) buffer, (b) endotoxin (10 micrograms/ml), (c) endotoxin + flunixin meglumine (10 micrograms/ml), or (d) calcium ionophore, A23187 (10 micrograms/ml). Thromboxane (TxB2), prostacyclin (6-keto-PGF1 alpha), and leukotriene C4 (LTC4) were determined in the incubation fluid by radioimmunoassay. Thromboxane and prostacyclin...