Topic:Arachidonic Acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid found in the phospholipids of cell membranes in horses. It serves as a precursor for the synthesis of eicosanoids, which include prostaglandins, thromboxanes, and leukotrienes. These eicosanoids are involved in various physiological processes, including inflammation and immune responses. In equine health, the metabolism of arachidonic acid and its derivatives can influence conditions such as laminitis, colic, and joint inflammation. This page compiles peer-reviewed research studies and scholarly articles that explore the metabolism, biological functions, and potential clinical implications of arachidonic acid in horses.
Evaluation of leukotriene biosynthetic capacity in lung tissues from horses with recurrent airway obstruction. To evaluate leukotriene (LT) biosynthetic capacity in lung tissue from healthy horses and horses with recurrent airway obstruction (RAO). Methods: Lung parenchyma and airway specimens from 8 RAO-affected and 5 healthy horses. Methods: Horses were stabled for > or = 72 hours. Blood was drawn before euthanasia, after which lung specimens were collected. Tissue strips from small airways and parenchyma were incubated in organ baths with the precursor LTA4 or stimulated with calcium ionophore A23187 or the tripeptide N-formyl-Met-Leu-Phe (fMLP), with or without exogenous arachidonic acid, in the...
Mammalian lipocalin-type prostaglandin D2 synthase in the fluids of the male genital tract: putative biochemical and physiological functions. Prostaglandin D2 synthase (PGDS) is a major epididymal secretory protein in several species. We quantified PGDS in ram and bull semen using a specific antiserum. Strong variations in PGDS concentration existed between animals. In the bull, the highest concentrations were found preferentially in animals with normal or high fertility, as was previously suggested. However, low concentrations were found in males with all ranges of fertility, suggesting that the function of PGDS either is not necessary for male fertility or can be assumed by other proteins when its concentration is low. In the ram ...
Purification, characterization, and cDNA sequencing of cytosolic phospholipase A(2) from equine neutrophils. It has been demonstrated that equine neutrophils, but not eosinophils, require exogenous arachidonic acid for calcium ionophore A23187-induced leukotriene synthesis. Because cytosolic phospholipase A(2) (cPLA(2)) plays an essential role in leukotriene formation in leukocytes, we investigated the presence of a functional cPLA(2) in equine neutrophils. To determine whether cPLA(2) from neutrophils was catalytically active, we purified the enzyme >6,500 fold with 3% recovery from equine neutrophils. The full-length cDNA sequence encoded a 749-amino acid protein. The deduced amino acid sequence...
Biphasic responses of equine colonic vessel rings to vasoactive inflammatory mediators. 1. The role of endothelium in modulating equine colonic vessel responses to histamine (HST), 5-hydroxytryptamine (5-HT), bradykinin (BK) and acetylcholine (ACh) was evaluated in vitro. 2. Segments of mesenteric arteries and veins were collected from the left ventral colon of six adult horses destined for euthanasia for reasons unrelated to cardiovascular or gastrointestinal systems. Vessels were gently cleansed and cut into 4 mm wide rings. 3. Three vessel conditions namely endothelium intact, endothelium removed and N omega-nitro-L-arginine methyl ester (L-NAME)-treated were used for both art...
Pharmacokinetics and pharmacodynamics of fenleuton, a 5-lipoxygenase inhibitor, in ponies. Leukotrienes, products of the 5-lipoxygenase pathway of arachidonic acid metabolism, possess properties consistent with their involvement in a range of inflammatory diseases. In this study the pharmacokinetics and pharmacodynamics of the selective 5-lipoxygenase inhibitor, fenleuton, have been examined in the horse. Orally administered fenleuton (four 5 mg kg(-1) doses, given once daily) was absorbed from the gastrointestinal tract, and penetrated readily into tissue cage exudate, the ratio of the plasma:exudate AUC0-48h being 0.90+/-0.02 (n=6). Ionophore-stimulated leukotriene (LT) B4 synthes...
A double-blind placebo-controlled trial of an evening primrose and fish oil combination vs. hydrogenated coconut oil in the management of recurrent seasonal pruritus in horses. Clinical status and plasma phospholipid fatty acids of 33 horses with seasonal pruritus were investigated following fatty acid supplementation. Principal areas affected by pruritus were mane, tail, head and rump. There were no significant differences in clinical status between horses receiving test and placebo capsules. Horses receiving the test preparation showed significant reduction (weeks 0-12) in linoleic acid (P < 0.05) and significant increases (weeks 0-24) in dihomogammalinolenic acid and alpha linolenic acid (P < 0.05). Placebo-treated horses showed significant reductions (wee...
Eicosanoid concentrations in digital venous blood from horses with chronic laminitis. The eicosanoids are a family of lipid-derived autocoids that are released in response to a variety of physical and hormonal stimuli. In this study, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were measured in the digital veins of clinically normal horses and horses with chronic laminitis to determine whether these arachidonic acid metabolites have a role in mediating signs of hoof pain and lesions associated with chronic laminitis. Horses were evaluated at rest and after a brief exercise period, to determine whether eicosanoids are released into the circulation after mild concussion. Dig...
Prostaglandin F2 alpha metabolite levels following an embryo transfer procedure in the mare. Hormonal, chemical, and mechanical stimuli can activate the arachidonic acid cascade and result in formation of prostaglandins and related substances. These compounds can have a profound role in the initiation of the inflammatory process (Higgins & Lees 1984). Prostaglandin (PG) F2α is the key hormone in reproductive physiology with well-known effects on reproductive performance e.g. luteolysis and abortion. An activation of the arachidonic acid cascade, caused by mechanical manipulation during an embryo transfer procedure, might be one explanation for early embryonic loss.
The effects of aspirin and paracetamol on the aggregation of equine blood platelets. The responses of equine blood platelets in citrated platelet-rich plasma to arachidonic acid, U44069 (prostaglandin endoperoxide analogue), adenosine 5'-diphosphate, platelet-activating factor or collagen were investigated by turbidimetric aggregometry. Pre-treatment of the platelets with aspirin (1 mmol/l) or paracetamol (1.3 mmol/l) abolished shape change and aggregation in response to arachidonic acid; decreased the rate of aggregation in response to collagen, with no separate effect on shape change; had no marked effect on aggregation caused by the other agonists; but in no case transforme...
Arachidonate metabolites in bronchoalveolar lavage fluid from horses with and without COPD. Arachidonate metabolites were measured in bronchoalveolar lavage fluid (BALF) from horses with (N = 4) and without (N = 7) chronic obstructive pulmonary disease (COPD). Prostaglandin (PG) D2, leukotriene (LT) B4 and LTC4 were present in highest concentrations in BALF from clinically normal horses. Concentrations of PGE2 and PGF were significantly higher in BALF from horses with COPD than in BALF from normal horses, but no differences were detected in thromboxane B2, 6-keto-PGF1 alpha, PGD2, LTB4 or LTC4.
Reduced endotoxin-induced production of tumor necrosis factor activity by equine peritoneal macrophages exposed to the dual inhibitor of arachidonic acid metabolism, SK & F 86002. The purpose of this study was to determine if a structurally novel dual inhibitor of arachidonic acid metabolism, SK & F 86002, would inhibit the endotoxin-induced production of tumor necrosis factor (TNF) activity by equine peritoneal macrophages. Equine peritoneal macrophages were variously pretreated for 0, 0.5 and 2 h with SK & F 86002 at 10(-9) to 10(-4) molar final concentrations or were left untreated. Then, the macrophages were cultured in vitro in the presence of endotoxin (5 ng/mL). Supernatant media were collected after 4 h and stored at -70 degrees C until assayed for TNF a...
Secretory activity of equine polymorphonuclear leukocytes: stimulus specificity and priming effects of bacterial lipopolysaccharide. Neutrophil (PMN) contributions to the acute inflammatory process and host defense include generation of bioreactive oxygen metabolites and secretion of granule enzymes. We assessed equine PMN secretion using several PMN stimuli, singly and in combination with bacterial lipopolysaccharide (LPS). LPS avidly associated with equine PMN, as shown by strong PMN labeling with FITC-conjugated LPS. LPS alone (1 or 10 micrograms ml-1) was a weak stimulus for PMN superoxide anion (O2-) generation, but preincubation with LPS followed by phorbol ester (PMA, 10 ng ml-1) significantly augmented (P less than ...
Epithelial strips: an alternative technique for examining arachidonate metabolism in equine tracheal epithelium. We have developed an alternative method for examining equine tracheal epithelial arachidonic acid (AA) metabolism that utilizes strips of pseudostratified columnar epithelium attached to a layer of elastic tissue 80 to 130 microns thick. We compared the responses of this preparation with those of enzymatically dispersed suspensions of tracheal epithelium obtained from the same animal. Strips incubated with [3H]AA incorporated 40.8 +/- 3.6% of added radioactivity and released 2.55 +/- 0.23% of incorporated radioactivity when stimulated with 5 microM A23187. Values for the cell suspension were 5...
Prostaglandin E2 secretion by oviductal transport-stage equine embryos. This study was conducted to identify embryonic products whose secretion was temporally associated with the oviductal transport period of the mare. Chemicals secreted by oviductal-transport-stage equine embryos were identified by incubating Day 6 or Day 7 early uterine embryos with 35S-methionine/cysteine, 3H-progesterone, or 3H-arachidonic acid for 24 h, and subsequently identifying radioactively labeled proteins (SDS-PAGE; n = 3 embryos), steroids (HPLC; n = 3 embryos), or prostaglandins (HPLC; n = 3 embryos) in the culture medium. Early uterine embryos secreted 116.1 +/- 45.5 pg of prostagla...
Endotoxemia in horses. A review of cellular and humoral mediators involved in its pathogenesis. Endotoxemia remains the leading cause of death in horses, being intimately involved in the pathogenesis of gastrointestinal disorders that cause colic and neonatal foal septicemia. Endotoxins, normally present within the bowel, gain access to the blood across damaged intestinal mucosa, or endotoxemia occurs when gram negative organisms proliferate in tissues. Endotoxins are removed from the circulation by the mononuclear phagocyte system, and the response of mononuclear phagocytes to these lipopolysaccharides (LPS) play an important role in determining the severity of clinical disease. Macroph...
Concentrations of arachidonate metabolites, steroids and histamine in preovulatory horse follicles after administration of human chorionic gonadotrophin and the effect of intrafollicular injection of indomethacin. This study investigated the sequence of hormonal changes within the preovulatory follicles of mares. Mares were injected i.v. with 2500 IU human chorionic gonadotrophin (hCG) when a preovulatory follicle of 35 mm in diameter was detected. Fluid was aspirated from preovulatory follicles before (0 h), and 12, 24 and 36 h after administration of hCG. Concentrations of progesterone, prostaglandin (PG) E2, PGF, 6-keto-PGF1 alpha and thromboxane B2 in follicular fluid increased significantly (P less than 0.01) between 0 and 36 h. At 36 h, PGE2 was present in highest concentrations, followed by PGF a...
Platelet function in the racing thoroughbred: implication for exercise-induced pulmonary hemorrhage. Platelet function was evaluated in horses with exercise-induced pulmonary hemorrhage (bleeder) and in control horses (nonbleeder). Platelet aggregation, secretion, and adhesion to rabbit aortic subendothelium were similar for bleeders and nonbleeders. Platelets readily aggregated in response to ADP, thrombin, collagen, and arachidonic acid, but platelet secretion occurred only with high concentrations of thrombin. Platelets readily adhered to rabbit aortic subendothelium and tended to form large thrombi rather than platelet monolayers or aggregates. These data suggest that horses may be predis...
Effects of indomethacin on neural and myogenic components in equine airway smooth muscle. Equine airway smooth muscle is innervated by vagal efferents and, in addition, displays spontaneous mechanical activity. The preparation thus appears to contain at least two discrete excitable components, the cholinergic neural elements and the smooth muscle membrane. Indomethacin (INDO), a cyclooxygenase (CO) inhibitor, exerts a considerable potentiation of function in this preparation. The latter may be effected indirectly, through loss of the inhibitory effect of endogenous prostaglandin E2 (PGE2) on neural acetylcholine release and through direct effects on smooth muscle of the generally a...
Effect of dietary linolenic acid on endotoxin-induced thromboxane and prostacyclin production by equine peritoneal macrophages. In laboratory animals, the incorporation of alpha linolenic acid or other n-3 series fatty acids into the diet results in marked changes in cell membrane composition as well as arachidonic acid metabolism. The purpose of the present study was to determine whether endotoxin-induced thromboxane A2 (TxA2) and/or prostacyclin (PGI2) production by equine peritoneal macrophages was altered by feeding horses a diet containing 8% linseed oil as a source of alpha linolenic acid for 8 weeks. Peritoneal macrophages were cultured in vitro in the presence of endotoxin (LPS) (0.5-500 ng/ml) or calcium ionop...
Release of immunoreactive arachidonate metabolites by equine endometrium in vitro. The ability of equine endometrium to release prostaglandin (PG) F, PGE2, and leukotriene (LT) B4 was studied in vitro, using endometrial tissue from diestrous mares. Because of the high cross-reactivity of the PGF antiserum with PGF1 alpha and with PGF2 alpha, results were quoted as total immunoreactive PGF. Significant concentrations of these arachidonate metabolites were released into tissue culture medium between 1 and 24 hours of incubation. Significantly higher concentrations of PGE, but not of PGE2 or LTB4, were released from endometria of mares with chronic endometritis than from genita...
The role of cyclooxygenase products in the acute airway obstruction and airway hyperreactivity of ponies with heaves. Airway obstruction and hyperreactivity are characteristics of human asthma and of "heaves," a naturally occurring respiratory disorder of horses and ponies. To document the role of cyclooxygenase products of arachidonic acid metabolism in the pathogenesis of heaves, we measured plasma and bronchoalveolar lavage (BAL) fluid concentrations of metabolites of thromboxane (TX)A2 and prostaglandins (PG) I2 and D2 in five affected ponies and their age- and gender-matched controls prior to and during acute airway obstruction precipitated by housing the ponies in a barn and exposing them to hay dust. P...
Platelet function testing in the pony. Platelet isolation techniques and platelet function were evaluated in 35 adult ponies. Platelet recovery from whole blood was consistent and the preparation of platelet rich plasma was facilitated by an enhanced erythrocyte sedimentation rate. All platelet samples aggregated in response to 10 microM ADP. However, concentrations of ADP as high as 100 microM did not elicit significant 14C-serotonin release. Collagen induced irreversible platelet aggregation and 14C-serotonin release in all samples. The threshold dose for collagen in most ponies was 1.5 micrograms. Arachidonic acid (500 microM) f...
Equine postanaesthetic myositis: thromboxanes, prostacyclin and prostaglandin E2 production. Arachidonic acid cyclooxygenase metabolites, thromboxane B2 (TXB2), prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1 (6-keto-PGF1) were measured in horses where anaesthesia was maintained with halothane. Two horses suffering from postanaesthetic myositis were compared with four normal horses. TXB2 and PGE2 levels were higher in mixed venous blood drawn from the myopathic horses. An increase of TXB2 and PGE2 levels appeared when myopathic horses were rolled into dorsal recumbency after a prolonged period of lateral recumbency. One hour after the end of anaesthesia, TXB2 had continued to incr...
Influence of arachidonic acid metabolites in vitro and in uterine washings on migration of equine neutrophils under agarose. The influence of arachidonic acid metabolites on migration of equine neutrophils under agarose was investigated. Leukotriene B4 (LTB4) was chemotactic at concentrations between 0.1 and 1000 ng ml-1 and prostaglandin E2 (PGE2) at 1 and 10 ng ml-1 but not at higher or lower concentrations. Prostaglandin F2 alpha (PGF2 alpha) was not chemotactic for equine neutrophils at any concentration. Random migration was significantly inhibited (P less than 0.05) by suspension of neutrophils in LTB4 (0.1 to 1000 ng ml-1) and PGF2 alpha (0.1 ng ml-1) but not at high concentrations. There was a significant po...
Central nervous system trauma. Traumatic injury to the central nervous system causes immediate damage and sets in motion a complex series of pathophysiologic events that result in further neuronal injury. This secondary damage seems to be related to changes in blood flow and pressure on a systemic, regional, and microvascular level. Currently, there is evidence that these changes are, in part, mediated by endogenous opioids and arachidonic acid metabolites, namely thromboxane A2. Medical management is generally designed to intervene at one or more stages in this secondary cascade of events. Further research should lead us t...
Applications of equine models of acute inflammation. The Ciba-Geigy Prize for Research in Animal Health. The development of reproducible models of acute inflammation in which inflammatory heat is easily quantified and from which inflammatory exudate is readily harvested has facilitated studies in the horse of the actions of steroids and non-steroidal anti-inflammatory drugs (NSAIDS). Blockade of the synthesis of eicosanoids and suppression of inflammatory heat by clinical dose rates of NSAIDS suggests a causal link between the two events and provides further evidence for a role of these compounds in acute equine inflammation. The tendency for enolic and carboxylic acids NSAIDS to accumulate in in...
Effects of flunixin meglumine, phenylbutazone and a selective thromboxane synthetase inhibitor (UK-38,485) on thromboxane and prostacyclin production in healthy horses. The efficacy of three agents which alter the metabolism of arachidonic acid was investigated in normal, conscious horses. A dose response evaluation was made of flunixin meglumine and phenylbutazone, two cyclo-oxygenase inhibitors, and of a selective thromboxane synthetase inhibitor, UK-38,485. Radioimmunoassay of thromboxane B2 (TxB2) and 6-keto prostaglandin F1 alpha (PGF1 alpha) was used to assess the concentrations of thromboxane A2 (TxA2) and prostacyclin (PGI2) respectively, in serum. Flunixin was the most potent inhibitor of serum TxB2 and 6-keto PGF1 alpha production. UK-38,485 also de...
Renal toxicity of non-steroidal anti-inflammatory drugs. Non-steroidal anti-inflammatory drugs represent the most heavily prescribed and used class of drugs in human medicine. Most are derivatives of either salicylates, propionic acid, indoleacetic acid, anthranilic acid, pyrazolone, or oxicams. They depress the synthesis of prostaglandins from arachidonic acid by reversible inhibition of the enzyme cyclooxygenase. In the kidney, prostaglandins PGE2 and PGI2 modulate the vasoconstrictor effects of angiotensin II, norepinephrine, and vasopressin. In the presence of volume contraction, anesthesia, or disease states associated with high levels of these...
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...
Stimulation of equine eosinophil migration by hydroxyacid metabolites of arachidonic acid. Lipoxygenase products of arachidonic acid are important mediators of inflammation, affecting several aspects of cell function. Monohydroxyeicosatetraenoic acid (mono-HETE) and 5,12-dihydroxyeicosatetraenoic acid (LTB4) enhance migration of both neutrophils and eosinophils in several species. The relative ability of positional isomers of HETE and of LTB4 to affect migration of equine eosinophils was studied. The 5, 8, 9, 11, 12, and 15 isomers of HETE were prepared by autooxidation of arachidonic acid, separated by sequential normal phase and reverse phase high performance liquid chromatography...