Prostaglandins are lipid compounds derived from fatty acids that are present in various tissues of horses. They are involved in a wide range of physiological processes, including the regulation of inflammation, blood flow, and reproductive functions. In equine medicine, prostaglandins are often studied for their role in modulating inflammatory responses and their potential therapeutic applications. These compounds can influence pain perception and are involved in processes such as parturition and the estrous cycle in mares. This page collects peer-reviewed research studies and scholarly articles that explore the synthesis, function, and clinical applications of prostaglandins in equine health.
Sikora M, Nowak M, Racheniuk H, Wojtysiak K, Kozdrowski R.Endometritis and endometrosis have been and still are the major reasons for infertility in mares. The diagnosis of endometritis can be based on cytology and microbiology, but endometrial biopsy is still the only way to diagnose endometrosis in the mare. Our study attempted to determine if a single biopsy using his-topathology and immunohistochemistry is sufficient to ascertain reasons for infertility in Icelandic mares. The objectives of this study were to examine the relationship between deviations in endometrial biopsies in terms of prostaglandin-endoperoxide synthase-2 (PTGS-2) and fibronec...
Martin EM, Jones SL.Inhibition of prostaglandin E2 (PGE2) production effectively limits inflammation in horses, however nonspecific prostaglandin blockade via cyclooxygenase (COX) inhibition elicits deleterious gastrointestinal side effects in equine patients. Thus, more selective PGE2 targeting therapeutics are needed to treat inflammatory disease in horses. One potential target is microsomal prostaglandin E-synthase-1 (mPGES-1), which is the terminal enzyme downstream of COX-2 in the inducible PGE2 synthesis cascade. This enzyme has yet to be studied in equine leukocytes, which play a pivotal role in equine inf...
Siemieniuch MJ, Gajos K, Kozdrowski R, Nowak M.Even if mares continue to breed up to an advanced age, in aging mares reproductive failure is quite common. Subclinical endometritis, which occurs more often in aging mares than in younger counterparts, may cause prolongation or shortening of the inter-estrus period or the corpus luteum lifespan. We hypothesized that during subclinical endometritis the secretion of selected arachidonic acid metabolites may differ in aging mares compared to younger females. To verify this thesis, ex vivo organ cultures of endometrium were established with subsequent measurements of concentrations of prostaglan...
Garcia-Muñoz A, Valldecabres-Torres X, Newcombe JR, Cuervo-Arango J, Garcia-Rosello E.The objective of this study was to determine the effect of exogenous progesterone administration at ovulation and during the early development of the CL, on its future sensitivity to a single administration of PGF2a in mares and cows. Horse Retrospective reproductive data from an equine clinic in the UK during three breeding seasons were used. Mares were divided into: control group, cycles with single ovulations; double ovulation group cycles with asynchronous double ovulations; and PRID group: cycles with single ovulations and treatment with intravaginal progesterone device (CIDR) immediately...
Pinto-Bravo P, Galvão A, Rebordão MR, Amaral A, Ramilo D, Silva E, Szóstek-Mioduchowska A, Alexandre-Pires G, Roberto da Costa R, Skarzynski DJ....The oviduct plays important roles in the early reproductive process. The aim of this study was to evaluate gene transcription and protein expression of progesterone receptor (PGR), estrogen receptors 1 (ESR1) and 2 (ESR2); oxytocin receptor (OXTR); prostaglandin F2α synthase (AKR1C3), and prostaglandin E2 synthase (Ptges) in mare oviduct in different estrous cycle stages. Estradiol (E), progesterone (P), oxytocin (OXT), and tumor necrosis factor α (TNF) effect on in vitro PGE and prostaglandin F2α (PGF) secretion by equine oviduct explants or by oviductal epithelial cells (OECs) were also ...
Bianco AW, Moore GE, Cooper BR, Taylor SD.Flunixin meglumine (FM) is a commonly used Nonsteroidal anti-inflammatory drug (NSAID) in horses, but clinical efficacy is often unsatisfactory. Ketorolac tromethamine (KT) demonstrates superior efficacy compared to other NSAIDs in humans, but its anti-inflammatory effects have not been investigated in the horse. Safety of repeated dosing of KT has not been evaluated. The first objective was to conduct a dose determination study to verify that a previously described dosage of KT would inhibit Lipopolysaccharide (LPS)-induced eicosanoid production in vitro, and to compare KT effects of this inh...
Kilborne AH, Hussein H, Bertone AL.OBJECTIVE To investigate effects of hyaluronic acid (HA) or HA combined with chondroitin sulfate (CS) and N-acetyl-d-glucosamine (NAG) by use of a lipopolysaccharide (LPS) in vitro method. SAMPLE Monolayer cultures of synovial cells from 4 adult horses. PROCEDURES Synovial cell cultures were untreated or treated with HA alone or HA-CS-NAG for 24 hours, subsequently unchallenged or challenge-exposed with 2 LPS concentrations (20 and 50 ng/mL) for 2 hours, and retreated with HA or HA-CS-NAG for another 24 hours. Cellular morphology of cultures was evaluated at 0, 24 (before LPS), 26 (after LPS),...
Frondoza CG, Fortuno LV, Grzanna MW, Ownby SL, Au AY, Rashmir-Raven AM.Objective Pro-inflammatory mediators such as prostaglandin E-2 (PGE2) play major roles in the pathogenesis of osteoarthritis (OA). Although current pharmacologic treatments reduce inflammation, their prolonged use is associated with deleterious side effects prompting the search for safer and effective alternative strategies. The present study evaluated whether chondrocyte production of PGE2 can be suppressed by the combination of avocado/soybean unsaponifiables (ASU) and α-lipoic acid (LA). Design Chondrocytes from articular cartilage of equine joints were incubated for 24 hours with: (1) con...
Leatherwood JL, Gehl KL, Coverdale JA, Arnold CE, Dabareiner RA, Walter KN, Lamprecht ED.Fourteen yearling Quarter horses (351 to 470 kg) were utilized in a randomized complete block design to evaluate potential of glucosamine hydrochloride (HCl) to mitigate intra-articular inflammation following a single inflammatory insult. Horses were blocked by BW, age, and sex, and randomly assigned to treatments for a 98-d experiment. Treatments consisted of a control diet (CON; = 7) fed 1% BW per d (as-fed) of concentrate only or a treatment diet ( = 7) of concentrate top dressed with 30 mg/kg BW glucosamine HCl (99.6% purity; GLU30) offered at 12 h intervals. Horses were maintained in indi...
Rebordão MR, Galvão A, Pinto-Bravo P, Pinheiro J, Gamboa S, Silva E, Mateus L, Ferreira-Dias G.Oxytocin (OXT) has been used to prolong the luteal phase in mares, but its mechanism of action is unknown. The aim of this study was to evaluate the effect of chronic exogenous OXT administration to mid-luteal phase mares on luteal maintenance. Also, endometrial expression of prostaglandin endoperoxide synthase 2 (PTGS2), prostaglandin Fα, E and I synthases (AKR1C3, PTGES, and PTGIS), oxytocin receptor (OXTR), progesterone receptor (PGR), and estrogen receptors 1 (ESR1) and 2 (ESR2) were assessed in mares experiencing luteal maintenance 2 weeks after chronic exogenous OXT administration. Con...
Mateu-Sánchez S, Newcombe JR, Garcés-Narro C, Cuervo-Arango J.The interval from both spontaneous and prostaglandin (PGF)-induced luteolysis to ovulation is greatly variable in mares. Several reports have shown a positive association between the length of the interval from PGF treatment to ovulation (ITO) and the subsequent pregnancy rate (PR). However, it is not known whether this association also occurs in estrous cycles with spontaneous luteolysis. The main objective of this study was to determine the effect of the duration of estrus-like echotexture of the uterus during the follicular phase on the subsequent PR in both spontaneous and PGF-induced cycl...
Klein C."Maternal recognition of pregnancy" (MRP) is commonly used to describe the ongoing embryo-maternal communication during early pregnancy that culminates in prevention of luteolysis and ensures ongoing progestin support. The conceptus-derived pregnancy recognition signal has not yet been identified in the mare. Although equine conceptuses produce substantial amounts of estrogens, there is a lack of evidence that estrogens are the pregnancy recognition signal in mares. Conceptus mobility is integral to MRP and is driven by conceptus-derived prostaglandin production. Cessation of conceptus mobilit...
Tangtrongsup S, Kisiday JD.Dexamethasone is known to support mesenchymal stem cell (MSC) chondrogenesis, although the effects of dose and timing of exposure are not well understood. The objective of this study was to investigate these variables using a laboratory model of MSC chondrogenesis. Methods: Equine MSCs were encapsulated in agarose and cultured in chondrogenic medium with 1 or 100 nM dexamethasone, or without dexamethasone, for 15 days. Samples were analyzed for extracellular matrix (ECM) accumulation, prostaglandin E2 and alkaline phosphatase secretion, and gene expression of selected collagens and catabolic e...
Kuhl J, Nagel C, Ille N, Aurich JE, Aurich C.In the present study we have evaluated a possible stress reaction in response to two different PGF2α analogs-luprostiol and D-cloprostenol--and their effects on estrous cycle characteristics. In a cross-over-design eight mares received in alternating order either luprostiol (Treatment LUP; 3.75 mg im), D-cloprostenol (Treatment CLO; 22.5μg im) or saline (Treatment CON; NaCl 0.9% 0.5ml im) on day 8 after ovulation. Injection of either LUP or CLO, but not of CON resulted in a significant decline of progesterone concentration in plasma to baseline concentrations within two days (time: p<0.00...
Martínez-Boví R, Cuervo-Arango J.The objectives were to determine: (i) whether intrafollicular administration of PGE2 and PGF2α to mares would hasten follicle collapse and (ii) the differences in reproductive hormone characteristics in mares with spontaneous and prostaglandin-induced follicle collapses. Six mares were followed for two oestrous cycles each: when the mares reached a follicle diameter of 30-35 mm and showed mild-to-moderate endometrial oedema, mares were administered a single 0.5 ml dose containing 500 μg PGE2 and 125 μg PGF2α (treatment cycle) or a placebo (0.5 ml of water for injection; control cycle) into...
Kozai K, Tokuyama S, Szóstek AZ, Toishi Y, Tsunoda N, Taya K, Sakatani M, Takahashi M, Nambo Y, Skarzynski DJ, Yamamoto Y, Kimura K, Okuda K.In mares, prostaglandin F2α (PGF2α) secreted from the endometrium is a major luteolysin. Some domestic animals have an auto-amplification system in which PGF2α can stimulate its own production. Here, we investigated whether this is also the case in mares. In an in vivo study, mares at the mid-luteal phase (days 6-8 of estrous cycle) were injected i.m. with cloprostenol (250 µg) and blood samples were collected at fixed intervals until 72 h after treatment. Progesterone (P4) concentrations started decreasing 45 min after the injection and continued to decrease up to 24 h (P < 0.05). In t...
Galvão A, Skarzynski D, Ferreira-Dias G.In the present work, we investigated the role of Nodal, an embryonic morphogen from the TGFβ superfamily in corpus luteum (CL) secretory activity using cells isolated from equine CL as a model. Expression pattern of Nodal and its receptors activin receptor A type IIB (ACVR2B), activin receptor-like kinase (Alk)-7, and Alk4, as well as the Nodal physiological role, demonstrate the involvement of this pathway in functional luteolysis. Nodal and its receptors were immune localized in small and large luteal cells and endothelial cells, except ACVR2B, which was not detected in the endothelium. Nod...
Clark KC, Kol A, Shahbenderian S, Granick JL, Walker NJ, Borjesson DL.Mesenchymal stem cell (MSC) therapy is being increasingly used to treat dogs and horses with naturally-occurring diseases. However these animals also serve as critical large animal models for ongoing translation of cell therapy products to the human market. MSC manufacture for clinical use mandates improvement in cell culture systems to meet demands for higher MSC numbers and removal of xeno-proteins (i.e. fetal bovine serum, FBS). While serum-free media (SFM) is commercially available, its affects on MSC phenotype and immunomodulatory functions are not fully known. The objective of this study...
Aurich C, Budik S.Early equine pregnancy shares many features with that of more intensively assessed domestic animals species, but there are also characteristic differences. Some of those are poorly understood. Descent of the equine conceptus into the uterine lumen occurs at day 5 to 6 after ovulation but is only possible when the embryo secretes prostaglandin E2. Although maintenance of equine pregnancy probably involves secretion of a conceptus derived anti-luteolytic factor, this agent has not been identified. Rapid growth, conceptus mobility and presence of an acellular capsule at the time of maternal recog...
Barton MH, Darden JE, Clifton S, Vandenplas M.To validate primer sets for use in reverse transcription quantitative PCR assays to measure gene expression of cytosolic phospholipase A2 (cPLA2) and microsomal prostaglandin E2 synthase 1 (mPGES1) in equine mononuclear cells and determine the effects of firocoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, on COX-2, cPLA2, and mPGES1 gene expression following incubation of mononuclear cells with lipopolysaccharide (LPS). Methods: 8 healthy adult horses. Methods: Peripheral blood mononuclear cells were isolated by density gradient centrifugation and incubated at 37°C with medium alone, f...
Ginther OJ, Castro T, Baldrighi JM, Wolf CA, Santos VG.Five mares that developed idiopathic persistent corpus luteum (PCL) were compared with 5 mares with apparently normal interovulatory intervals (IOIs). Progesterone (P4) and a metabolite of prostaglandin F2α (PGFM) were assayed daily beginning on the day of ovulation (Day 0). Transition between the end of an initial progressive P4 increase and the beginning of a gradual decrease in P4 occurred on mean Day 6. The gradual decrease in P4 between Days 6 and 12 was less (approached significance, P < 0.06) in the PCL group than in the IOI group. The P4 concentration on Day 12 (before luteolysis i...
Geisert RD.Establishment and maintenance of pregnancy in a number of mammalian species depends upon a tightly regulated interaction between the semiallogeneic conceptus and the maternal uterine endometrium.The term "Maternal Recognition of Pregnancy" is attributed to Roger V. Short's paper titled "Implantation and the Maternal Recognition of Pregnancy" which was published in proceedings from the 1969 Symposium on Foetal Autonomy.Professor Short's landmark paper stimulated increased interest in elucidating how the conceptus signals its presence to assure maintenance of the corpus luteum beyond the normal ...
Klein C.Few, if any, biological processes are as diverse among domestic species as establishment of early pregnancy, in particular maternal recognition of pregnancy. Following fertilization and initial development in the mare oviduct, selective transport of the embryo through the uterotubal junction driven by embryo-derived PGE2 occurs. Upon arrival in the uterus, an acellular glycoprotein capsule is formed that covers the embryo, blastocyst, and conceptus (embryo and associated extraembryonic membranes) between the second and third weeks of pregnancy. Between Days 9 and 15/16 of pregnancy, the concep...
de Ruijter-Villani M, Stout T.Implantation is a pivotal step in the establishment of mammalian pregnancy. Although implantation strategies vary between species, many aspects of conceptus-maternal signalling necessary to induce uterine receptivity to implantation are conserved. The temporal 'window' for the initiation of implantation is short and precisely controlled by endocrine, paracrine and autocrine factors. An invariable prerequisite for the development of uterine receptivity to implantation is continuous exposure of the endometrium to progesterone which, after a species-specific interval, downregulates progesterone r...
Moraes AP, Moreira JJ, Brossi PM, Machado TS, Michelacci YM, Baccarin RY.This study aimed to verify whether transient inflammatory reactions incited by the administration of intra-articular platelet-rich plasma (PRP) affected joint components through short- and long-term in vivo evaluation of inflammatory biomarkers and extracellular matrix degradation products in synovial fluid. The effects of PRP were analyzed in a short phase protocol (SPP) and in a prolonged phase protocol (PPP), using saline-injected joints as controls. In the SPP, higher white blood cell counts and prostaglandin E2 and total protein concentrations were observed in the synovial fluid of PRP-tr...
Ross-Jones TN, McIlwraith CW, Kisiday JD, Hess TM, Hansen DK, Black J.Dietary n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation has previously been shown to modify joint-related inflammation in several species, although information in the horse is lacking. We investigated whether dietary supplementation with n-3 LCPUFA would modify experimentally induced synovitis in horses. Twelve, skeletally mature, non-pregnant mares were randomly assigned to either a control diet (CONT) or an n-3 long-chain fatty acid-enriched treatment diet (N3FA) containing 40 g/day of n-3 LCPUFA for 91 days. Blood samples taken on days 0, 30, 60 and 90, and synovial flu...
Gajos K, Kozdrowski R, Nowak M, Siemieniuch MJ.Mares that fail to become pregnant after repeated breeding, without showing typical signs of clinical endometritis, should be suspected of subclinical endometritis (SE). Contact with infectious agents results in altered synthesis and secretion of inflammatory mediators, including cytokines and arachidonic acid metabolites, and disturbs endometrial functional balance. To address the hypothesis that SE affects the immune endocrine status of the equine endometrium, spontaneous secretion of prostaglandin E(2) (PGE(2)), prostaglandin F(2α) (PGF(2α)), 6-keto-PGF(1α )(a metabolite of prostacyclin ...
Duz M, Parkin TD, Cullander RM, Marshall JF.To evaluate ex vivo cyclooxygenase (COX) inhibition and compare in vitro and ex vivo COX-1 inhibition by flunixin meglumine and firocoxib in horses. Methods: 4 healthy horses for in vitro experiments and 12 healthy horses (6 males and 6 females; 5 Thoroughbreds, 5 Warmbloods, and 2 ponies) undergoing elective surgery for ex vivo experiments. Methods: 12 horses received flunixin meglumine (1.1 mg/kg, IV, q 12 h) or firocoxib (0.09 mg/kg, IV, q 24 h). Blood samples were collected before (baseline) and 2 and 24 hours after NSAID administration. Prostanoids (thromboxane B2, prostaglandin E2, and p...
Martínez-Boví R, Cuervo-Arango J.Haemorrhagic anovulatory follicle is the most common pathological anovulatory condition in the mare, but its cause remains unknown. An experimental model to induce luteinised unruptured follicles (LUF) with flunixin-meglumine (FM) has been developed. Luteinised unruptured follicles share similar morphological and hormonal characteristics with haemorrhagic anovulatory follicles. Objective: To test the effect of intrafollicular administration of prostaglandins PGE2 and PGF2α during the periovulatory period on ovulation and pregnancy in FM-treated mares. Methods: In vivo experiment in a crossove...
Kim TW, Della Rocca G, Di Salvo A, Ryschanova R, Sgorbini M, Giorgi M.To determine the pharmacokinetics of cimicoxib and to assess the inhibition of cyclooxygenase (COX) after a 5 mg/kg, single oral administration in horses that were fasted or fed. Methods: The study was conducted using an open, single dose (5 mg/kg), two treatment (fasted and fed), two-period, crossover design with a 2-week interval between dosages. Six healthy mares received 5 mg/kg of cimicoxib via nasogastric tube after fasting for 12 hours, or 2 hours after feeding. After administration, blood samples were collected for up to 24 hours and plasma used for pharmacokinetic analysis. Addi...
de Ruijter-Villani M, Stout T.Implantation is a pivotal step in the establishment of mammalian pregnancy. Although implantation strategies vary between species, many aspects of conceptus-maternal signalling necessary to induce uterine receptivity to implantation are conserved. The temporal 'window' for the initiation of implantation is short and precisely controlled by endocrine, paracrine and autocrine factors. An invariable prerequisite for the development of uterine receptivity to implantation is continuous exposure of the endometrium to progesterone which, after a species-specific interval, downregulates progesterone r...
Meyers KM, Lindner C, Katz J, Grant B.Nonsteroidal anti-inflammatory drugs impair platelet aggregation and secretion in man, pigs, and rabbits and inhibit platelet thromboxane/prostaglandin synthesis. The present investigation studied the effects of phenylbutazone on platelet aggregation and bleeding times in the horse. Aggregation responses to adenosine diphosphate and collagen were markedly impaired 15 minutes and 2 hours after treatment, but 4 hours after treatment, platelet responses approximated those prior to treatment. The in vivo effect of phenylbutazone correlated with its plasma concentrations. Phenylbutazone, like aspir...
Stout TA, Lamming GE, Allen WR.Recent evidence indicates that, in mares, as in the domestic ruminants, oxytocin and its endometrial receptor play important roles in stimulating the pulsatile releases of prostaglandin F2 alpha from the endometrium that effect luteolysis. In the present experiment, continuous administration of oxytocin by subcutaneous minipump to five mares during days 8-20 after ovulation abolished luteolysis in four of them, while all four of the control mares infused similarly with saline underwent luteolysis at the expected time. When oxytocin administration began on day 10, instead of on day 8, after ovu...
Kindahl H, Knudsen O, Madej A, Edqvist LE.Blood samples from 4 mares during the late luteal phase, oestrus, early pregnancy and up to about 150 days of gestation were analysed for 15-keto-13,14-dihydroprostaglandin F-2 alpha (PGFM), progesterone, PMSG and oestrone sulphate by radioimmunoassays. During the late luteal phase, at the time of corpus luteum regression and decreasing progesterone levels, PGFM peaks were recorded. During early pregnancy (i.e. from mating and up to about Day 30) no such peaks were detected. After mating the progesterone levels increased and remained high throughout the observation period. During the oestrous ...
Ferreira-Dias G, Costa AS, Mateus L, Korzekwa AJ, Galvão A, Redmer DA, Lukasik K, Szóstek AZ, Woclawek-Potocka I, Skarzynski DJ.Cytokines and nitric oxide (NO) are potential mediators of luteal development and maintenance, angiogenesis, and blood flow. The aim of this study was to evaluate (i) the localization and protein expression of endothelial and inducible nitric oxide synthases (eNOS and iNOS) in equine corpora lutea (CL) throughout the luteal phase and (ii) the effect of a nitric oxide donor (spermine NONOate, NONOate) on the production of progesterone (P4) and prostaglandin (PG) E(2) and factor(s) that stimulate endothelial cell proliferation using equine luteal explants. Luteal tissue was classified as corpora...
Roger T, Ruckebusch Y.The motor responses of the caecum and colon to stimulation of alpha 2-adrenoceptors by xylazine and detomidine at the recommended dose levels of 0.6 and 0.1 mg/kg were investigated in three ponies. The motor changes of the left ventral colon induced by continuous intra-arterial infusion of a prostaglandin (PGF2 alpha) were used to assess the relative inhibitory effects of xylazine and detomidine in a colic model. The administration of alpha 2-agonists inhibited the spiking activity on the whole of the large intestine for 20-30 min (xylazine) or 2-3 h (detomidine). However, the detomidine-induc...
Machado TSL, Massoco CO, Silva LCLC, Fülber J, Moreira JJ, Baccarin RYA.To compare effects of platelet-rich plasma (PRP), interleukin-1 receptor antagonist protein (IRAP), autologous processed plasma (APP), and sodium hyaluronate treatments on synovial fluid cells in vitro and on synovial fluid obtained from osteochondrotic joints of horses. Methods: Synovial fluid cells from 8 healthy equine tibiotarsal joints (in vitro experiment) and synovial fluid samples from 40 tibiotarsal joints of 25 horses with osteochondrosis dissecans (in vivo experiment). Methods: Effects of various treatments on concentrations of prostaglandin (PG) E2, interleukin (IL)-1β, tumor necr...
Cook VL, Jones Shults J, McDowell MR, Campbell NB, Davis JL, Marshall JF, Blikslager AT.To investigate effects of lidocaine hydrochloride administered IV on mucosal inflammation in ischemia-injured jejunum of horses treated with flunixin meglumine. Methods: 24 horses. Methods: Horses received saline (0.9% NaCl) solution (SS; 1 mL/50 kg, IV [1 dose]), flunixin meglumine (1 mg/kg, IV, q 12 h), lidocaine (bolus [1.3 mg/kg] and constant rate infusion [0.05 mg/kg/min], IV, during and after recovery from surgery), or both flunixin and lidocaine (n = 6/group). During surgery, blood flow was occluded for 2 hours in 2 sections of jejunum in each horse. Uninjured and ischemia-injured jejun...
Shrestha HK, Beg MA, Burnette RR, Ginther OJ.Horses are about five times more sensitive to the luteolytic effect of prostaglandin F2alpha (PGF) than cattle, as indicated by a recommended clinical dose of 5 mg in horses and 25 mg in cattle. Novel evaluations of the PGF plasma disappearance curves were made in mares and in heifers, and the two species were compared. Mares and heifers (n = 5) of similar body weight were injected (Min 0) intravenously with PGF (5 mg per animal). Blood was sampled every 10 sec until Min 3, every 30 sec until Min 5, every 10 min until Min 60, and every 30 min until Min 240. The mean PGF concentration was great...
Van de Water E, Oosterlinck M, Korthagen NM, Duchateau L, Dumoulin M, van Weeren PR, Olijve J, van Doorn DA, Pille F.An established lipopolysaccharide (LPS) model previously described in Warmbloods, was inconsistent in Standardbred horses, where lameness was not detected despite the presence of synovitis. The present study aimed to determine the dose of LPS from E. coli O55:B5 required to induce mild to moderate lameness following middle carpal joint injection in Standardbred horses and to quantitate the induced lameness over time, with and without anti-inflammatory pre-treatment. In a baseline trial, eight healthy, clinically sound Standardbred horses were used in a rule-based dose-escalation design trial, ...
Szóstek AZ, Siemieniuch MJ, Galvão AM, Lukasik K, Zieba D, Ferreira-Dias GM, Skarzynski DJ.Cell cultures are useful for determining the responses of specific cell types to various factors under controlled conditions and for obtaining a better understanding of in vivo physiologic processes. The aims of the present study were (i) to establish methodologies for isolation, culture and cryopreservation of equine endometrial epithelial and stromal cells; and (ii) to determine the effect of passage and cryopreservation on endometrial cell physiology, based on their basal and oxytocin (OT)-stimulated prostaglandin (PG) release. Epithelial and stromal cells were obtained by enzymatic digesti...
Bottoms GD, Templeton CB, Fessler JF, Johnson MA, Roesel OF, Ewert KM, Adams SB.This study had 2 objectives: (i) to correlate plasma thromboxane and prostaglandin I2 (epoprostenol) concentrations with hemodynamic changes occurring in equine endotoxin shock, and (ii) to determine the effects of flunixin meglumine on plasma concentrations of these prostaglandins relative to hemodynamic changes. Shock was induced in 2 groups, each of 4 anesthetized ponies, and in a 3rd group of 2 ponies. Group A ponies were given endotoxin only (and were not treated), and group B ponies were given endotoxin and then treated with flunixin meglumine. Group C ponies were treated with flunixin m...
Ginther OJ, Beg MA.The profile of circulating progesterone concentration is more dynamic in cattle than in horses. Greater prominence of progesterone fluctuations in cattle than in horses reflect periodic interplay in cattle between pulses of a luteotropin (luteinizing hormone; LH) and pulses of a luteolysin (prostaglandin F2alpha; PGF2alpha). A dose of PGF2alpha that induces complete regression of a mature corpus luteum with a single treatment in cattle or horses is an overdose. The overdose effects on the progesterone profile in cattle are an immediate nonphysiological increase taking place over about 30 min, ...
Silver M, Fowden AL.The production of uterine PGFM during different dietary states has been investigated in pregnant mares in late gestation. Arterial and uterine venous plasma concentrations of PGFM rose when food was withdrawn for 12-30 h and the V-A difference widened significantly. There was an inverse correlation between the rise in PGFM and the fall in plasma glucose during a fast, and a significant decrease in the A-V plasma glucose differences across the uterus. Plasma PGFM and free fatty acid concentrations before and during food withdrawal were also correlated but no uterine A-V difference in free fatty...
Moreira JJ, Moraes AP, Brossi PM, Machado TS, Michelacci YM, Massoco CO, Baccarin RY.This experimental controlled study was performed to evaluate the composition of autologous processed plasma (APP), and the effects of APP intra-articular injection into healthy equine metacarpophalangeal joints. The effects on joints were analysed with a short-phase protocol and a prolonged-phase protocol using saline-injected joints as controls. For the short protocol, horses received one intra-articular APP injection. Synovial fluid samples were collected prior to the injection and 3, 6, 24, 48, and 16 h after treatment. For the prolonged protocol, the joints received three weekly injections...
Collins LG, Tyler DE.Phenylbutazone (PBZ) toxicosis was induced in 9 ponies to further define the clinical and pathologic changes occurring with this syndrome. Six additional ponies were treated with PBZ and a synthetic prostaglandin E2 to determine the role of prostaglandins in the pathogenesis of PBZ toxicosis. Ponies given only PBZ exhibited CNS depression, anorexia, weight loss, diarrhea, cyanotic mucous membranes, and oral ulcers. Total serum protein concentration gradually decreased during the 10-day treatment period. Marked mucosal atrophy, focal erosions, and ulcers characterized the lesions in the aliment...
Szóstek AZ, Adamowski M, Galvão AM, Ferreira-Dias GM, Skarzynski DJ.Tumor necrosis factor-α (TNF) is a cytokine that plays important roles in functions of the endometrium. The aims of this study were to determine whether (i) ovarian steroids modulate TNF production by endometrial cells (Experiment 1); (ii) TNF effects on prostaglandin (PG) production in cultured equine endometrial cells and tissue (Experiment 2). Epithelial and stromal cells were isolated from equine endometrium (Days 2-5 of the estrous cycle; n=20) and treated after passage 1. In Experiment 1, epithelial and stromal cells were exposed to progesterone (P4; 10(-7)M), 17-β estradiol (E2; 10(-9...
Rivera Del Alamo MM, Reilas T, Kindahl H, Katila T.Intrauterine glass balls are used to prevent oestrous signs in sports mares, but the mechanism of action is unknown. It has been suggested that the glass ball can mimic an embryo or act via an induced chronic uterine inflammation and absent or continuous low-grade prostaglandin (PG) release. The purpose of this study was to induce prolonged luteal function in mares using a small intrauterine device (IUD) and to study the mechanisms behind prolonged IUD-induced luteal function. A uterine swab and a biopsy specimen were obtained in early oestrus. A water-filled plastic ball, diameter 20mm and we...
Bottoms GD, Johnson MA, Lamar CH, Fessler JF, Turek JJ.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...
Galvao AM, Ramilo DW, Skarzynski DJ, Lukasik K, Tramontano A, Mollo A, Mateus LM, Ferreira-Dias GM.Proapoptotic factor Fas ligand (FASL) and its cell surface receptor FAS are tumor necrosis factor superfamily members that trigger apoptosis in different cell types. However, their influence on luteal steroidogenesis is not clearly understood. The aim of the present work was to determine (i) the presence of the cytokine FASL and its receptor FAS in the mare's corpus luteum (CL) throughout the luteal phase, as well as (ii) the influence of FASL alone, or together with the cytokines tumor necrosis factor alpha (TNF) and interferon gamma (IFNG), on equine luteal cell production of luteotrophic an...
Martínez Aranzales JR, Cândido de Andrade BS, Silveira Alves GE.Phenylbutazone (PBZ) is widely used in equine medicine, and its side effects on the gastrointestinal tract are well known. The inhibition of prostaglandins and the oxidative stress induced by nonsteroidal anti-inflammatory drugs (NSAIDs) are described as mechanisms of gastric mucosal injury in humans. In horses, only the secondary effect of changes in cyclooxygenases is related to gastric mucosal injury. The objective of this study was to evaluate the effect of PBZ on certain antioxidative/oxidative parameters of the gastric mucosa. The concentrations of antioxidants and oxidants (superoxide d...
Peroni JF, Moore JN, Noschka E, Grafton ME, Aceves-Avila M, Lewis SJ, Robertson TP.Equine laminitis is a crippling condition associated with a variety of systemic diseases. Although it is apparent that the prodromal stages of laminitis involve microvascular dysfunction, little is known regarding the physiology of this vasculature. The aim of the present study was to determine the relative responses of equine laminar arteries and veins to the vasoconstrictor agonists phenylephrine (1 nM-10 microM), 5-HT (1 nM-10 microM), PGF2alpha (1 nM-100 microM), and endothelin-1 (1 pM-1 microM). We have determined that laminar veins were more sensitive, with respect to the concentration o...
Gibson KT, Hodge H, Whittem T.Enzyme immunoassay for prostaglandin E2 (PGE2), and radioimmunoassays for prostaglandin F2 alpha (PGF2 alpha), 6-keto-PGF1 alpha, and leukotriene B4 (LTB4) were performed on synovial fluid from normal middle carpal joints of 10 horses, and from 30 middle carpal or antebrachiocarpal joints of horses affected by degenerative joint disease and chip fractures to compare the concentrations of inflammatory mediators. Significantly greater concentrations of PGE2 were detected in fluid from affected than from control joints, but there were no significant differences in the mean concentrations of PGF2 ...
Galvão A, Wolodko K, Rebordão MR, Skarzynski D, Ferreira-Dias G.In the present report we describe the involvement of transforming growth factor B1 (TGF) in functional regression and structural luteolysis in the mare. Firstly, TGF and its receptors activin-like kinase (ALK) 5 and TGF receptor 2 were identified in corpus luteum (CL) steroidogenic, endothelial and fibroblast-like cells. Also, TGF and ALK5 protein expression were shown to be increased in Mid-, and Late-CL (p < 0.05). Subsequently, using an in vitro model with Mid-CL cells, we studied the role of TGF on secretory activity and cell viability. Cell treatment with TGF decreased progesterone...
Koblischke P, Kindahl H, Budik S, Aurich J, Palm F, Walter I, Kolodziejek J, Nowotny N, Hoppen HO, Aurich C.We tested the hypothesis that subclinical endometritis occurs after embryo transfer (ET) in the horse. Recipient mares were treated with meclofenamic acid (M) or flunixin meglumin (F) after ET or were left untreated (n=9 per group). Embryos were re-collected 4 days after transfer. Endometrial biopsies were taken for histology and analysis of cyclooxygenase-2 (COX-2) by immunohistochemistry and for PCR. Bacteriological swabs were collected from the uterus and lavage fluid of donor and recipient mares. Progesterone and prostaglandin F(2alpha) release was analysed in recipient mares after ET. Fou...
Leatherwood JL, Gehl KL, Coverdale JA, Arnold CE, Dabareiner RA, Walter KN, Lamprecht ED.Fourteen yearling Quarter horses (351 to 470 kg) were utilized in a randomized complete block design to evaluate potential of glucosamine hydrochloride (HCl) to mitigate intra-articular inflammation following a single inflammatory insult. Horses were blocked by BW, age, and sex, and randomly assigned to treatments for a 98-d experiment. Treatments consisted of a control diet (CON; = 7) fed 1% BW per d (as-fed) of concentrate only or a treatment diet ( = 7) of concentrate top dressed with 30 mg/kg BW glucosamine HCl (99.6% purity; GLU30) offered at 12 h intervals. Horses were maintained in indi...
Galvão A, Tramontano A, Rebordão MR, Amaral A, Bravo PP, Szóstek A, Skarzynski D, Mollo A, Ferreira-Dias G.Metabolic hormones have been associated with reproductive function modulation. Thus, the aim of this study was: (i) to characterize the immunolocalization, mRNA and protein levels of leptin (LEP), Ghrelin (GHR) and respective receptors LEPR and Ghr-R1A, throughout luteal phase; and (ii) to evaluate the role of LEP and GHR on progesterone (P4), prostaglandin (PG) E2 and PGF2α , nitric oxide (nitrite), tumor necrosis factor-α (TNF); macrophage migration inhibitory factor (MIF) secretion, and on angiogenic activity (BAEC proliferation), in equine corpus luteum (CL) from early and mid-luteal sta...
Macpherson ML, Giguère S, Pozor MA, Burden CA, Berghaus LJ, Berghaus RD, Varner JC, Hayna JT, Benson SM, Randell SA, Lyle SK, Kelleman AA, Hart KA....Minimal evidence exists supporting therapeutic selections for equine placentitis. The goal of this study was to characterize the anti-inflammatory effects of firocoxib when administered to mares with placentitis. Mares (gestation D270-300) were assigned to: INFECT (n = 6; placentitis, no treatment), FIRO (n = 6; placentitis, firocoxib, 0.1 mg/kg, PO, daily), and NORM (n = 6; no infection/treatment). Allantoic fluid (8 hours, 24 hours, birth) and amniotic fluid (birth) were collected from mares after infection. Concentrations of IL-1β, IL-6, TNF-α, IL-10, PGF , and PGE in fluids were...
Morton AJ, Campbell NB, Gayle JM, Redding WR, Blikslager AT.Synovitis in horses is frequently treated by administration of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase isoforms (COX-1 and COX-2). Constitutively expressed COX-1 is involved in physiologic functions such as maintenance of gastric mucosal integrity, whereas COX-2 is up-regulated at sites of inflammation. Thus, COX-2 inhibitors reduce inflammation with reduced gastrointestinal side effects as compared to non-selective COX inhibitors. The objective of the present study was to compare the anti-inflammatory effects of the preferential COX-2 inhibitor etodolac wi...
Moses VS, Hardy J, Bertone AL, Weisbrode SE.To evaluate the effects of anti-inflammatory drugs on lipopolysaccharide (LPS)-challenged and -unchallenged equine synovial membrane in terms of production of prostaglandin E2 (PGE2) and hyaluronan, viability, and histomorphologic characteristics. Methods: Synovial membranes were collected from the carpal, tarsocrural, and femoropatellar joints of 6 adult horses. Methods: Synovial membranes from each horse were minced and pooled and explants were treated with one of the following: no drug (control), drug, LPS alone, or LPS and drug. Treatment drugs were phenylbutazone (PBZ), flunixin meglumine...
