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.
Ibrahim S, Szóstek-Mioduchowska A, Skarzynski D.Bacterial infections of the genital tract are the major cause of reproductive failure in the mares. MiRNAs are important regulators of gene expression, mostly through transcriptional and translational regression. We hypothesized that LPS induced aberrant expression of miRNAs and their targets, which are involved in regulation of uterine homeostasis. Three groups of primary endometrial epithelial and stromal cells, and endometrial tissue explants were cultured. The 1 group was kept as control, while the 2 and 3 groups were challenged with low (0.5 μg/mL) or high (3.0 μg/mL) doses of Lipop...
Kouba JM, Burns TA, Webel SK.The effects of dietary marine-derived n-3 fatty acids (FA) on mare milk and mare and foal plasma FA, postpartum ovarian follicular growth and prostaglandin concentrations were evaluated. Sixty days prior to expected foaling dates, mares were assigned to one of three diets: corn oil (CORN, n = 6), docosahexaenoic acid (DHA) diet (D; 12.64 g/d, n = 7), or eicosapentaenoic acid (EPA) and DHA (ED; 8.84 g EPA, 10.43 g DHA/d, n = 7). Milk and plasma were collected for FA analysis. Follicular data were recorded through the first postpartum ovulation. Post-ovulation serial blood samp...
Schwarzbach SV, Melo CF, Xavier PLP, Roballo KC, Cordeiro YG, Ambrósio CE, Fukumasu H, Carregaro AB.Osteoarthritis (OA) is one of the main locomotor disorders in horses. Although nonsteroidal anti-inflammatory drugs are the first-line treatment for OA, opioids could also be used. In previous studies, opioids showed promising anti-inflammatory and analgesic effects. In this study, we aimed to investigate the effects of two opioids (morphine and methadone) against inflammation in lipopolysaccharide (LPS)-stimulated synoviocytes by analyzing microsomal prostaglandin E synthase-1 (mPGES-1) and prostaglandin-endoperoxide synthase 2 (PTGS2) expression. Synoviocytes were obtained from the joints at...
Bonometti S, Menarim BC, Reinholt BM, Ealy AD, Johnson SE. To provide insight into maternal recognition of pregnancy control in equids, the mitogenic and developmental effects of endometrium-expressed growth factors (epidermal growth factor (EGF), fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1)) were examined in equine iTr cells, an equine trophectoderm cell line. Initial western blots revealed that HGF and IGF-1 stimulate phosphorylation of AKT serine/threonine kinase 1 (AKT1) and EGF, FGF2, or HGF resulted in phosphorylation of both extracellular signal-regulated kinase 1 (ERK1) and ERK2...
Rebordão MR, Amaral A, Lukasik K, Szóstek-Mioduchowska A, Pinto-Bravo P, Galvão A, Skarzynski DJ, Ferreira-Dias G.Prostaglandin E (PGE) has contradictory effects in many organs. It may have proinflammatory, anti-inflammatory, or anti-fibrotic roles, depending on the type of receptors to which it binds. By signaling through its receptors EP2 and EP4, PGE mediates anti-inflammatory and anti-fibrotic actions. In spite of chronic endometrial fibrosis (endometrosis) being a major cause of mare infertility, its pathogenesis is not fully understood. We have shown that contact of mare endometrium in vitro with neutrophil extracellular traps (NETs) proteases favors endometrial collagen type I production. Therefor...
Nash DM, Paddison J, Davies Morel MCG, Barnea ER.Persistent mating-induced endometritis (PMIE) is a significant cause of mare infertility hence its treatment would advance the management of susceptible mares. Preimplantation factor (PIF) is secreted by viable embryos, including human, mouse and cattle, and is essential for maternal immune-tolerance without immune-suppression by modulating inflammation. This preliminary study aimed to test whether PIF exerts inflammatory-modulating properties upon equine endometrium challenged with Escherichia coli-derived lipopolysaccharide (LPS) using endometrial explant culture. Follicular (n = 3), lutea...
Scaravaggi I, Borel N, Romer R, Imboden I, Ulbrich SE, Zeng S, Bollwein H, Bauersachs S.Previous endometrial gene expression studies during the time of conceptus migration did not provide final conclusions on the mechanisms of maternal recognition of pregnancy (MRP) in the mare. This called for a cell type-specific endometrial gene expression analysis in response to embryo signals to improve the understanding of gene expression regulation in the context of MRP. Laser capture microdissection was used to collect luminal epithelium (LE), glandular epithelium and stroma from endometrial biopsies from Day 12 of pregnancy and Day 12 of the oestrous cycle. RNA sequencing (RNA-Seq) showe...
Amaral A, Fernandes C, Lukasik K, Szóstek-Mioduchowska A, Baclawska A, Rebordão MR, Aguiar-Silva J, Pinto-Bravo P, Skarzynski DJ, Ferreira-Dias G.We have shown that bacteria induce neutrophil extracellular traps (NETs) in mare endometrium. Besides killing pathogens, NETs may contribute for endometrosis (chronic endometrium fibrosis). Since elastase (ELA) is a NETs component that regulates fibrosis and prostaglandin (PG) output, the aim was to evaluate if inhibition of ELA would affect collagen 1 (COL1) transcription and PGs secretion by endometrium explants, in different estrous cycle phases. Follicular-FP (n = 8) and mid luteal-MLP (n = 7) phases explants were cultured for 24-48 hr with medium alone (Control), ELA (0.5 μg/ml,1 ...
Ross KA, Kolb DS, Macedo A, Anderson M, Klein C.This study tested the hypothesis that the presence of prostaglandin E2 in seminal plasma would aid in the transport of phenolsulfonphthalein (PSP) across the uterotubal junction. Five mares in estrus were inseminated during estrus with PSP dissolved in phosphate-buffered saline and during the subsequent estrus with PSP added to a standard insemination dose. Serum and urine samples were obtained at hours 0, 1, 2, and 3 following treatment and examined for the presence of PSP. Phenolsulfonphthalein could not be detected in any of the urine samples collected from mares following either treatment....
Pye J, Clulow J, Adkins A.To describe the laparoscopic transection of restrictive bands of the mesosalpinx as a useful adjunct to the topical application of prostaglandin E to treat mares with suspected uterine tubal blockage. Methods: A standard left flank laparoscopic approach was made to the abdomen using three laparoscopic portals. If restrictive bands of the mesosalpinx were observed traversing the uterine tube perpendicularly, they were carefully transected and 1 mg of prostaglandin E was then applied to the external surface of the uterine tube. Skin incisions were closed with surgical staples and the procedure...
Vendruscolo CDP, Moreira JJ, Seidel SRT, Fülber J, Neuenschwander HM, Bonagura G, Agreste FR, Baccarin RYA.The aim of this study was to verify whether transient inflammatory reactions induced by intra-articular medicinal ozone administration affect joint components, by in vivo evaluation of inflammatory (prostaglandin E2, Substance P, Interleukin-6, Interleukine-1, Tumor Necrosis Factor), anti-inflammatory (Interleukin-10) and oxidative (superoxide dismutase activity and oxidative burst) biomarkers and extracellular matrix degradation products (chondroitin sulphate and hyaluronic acid) in synovial fluid. The effects of medicinal ozone were analyzed at two ozone concentrations (groups A and B, 20 an...
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...
Smits K, Willems S, Van Steendam K, Van De Velde M, De Lange V, Ververs C, Roels K, Govaere J, Van Nieuwerburgh F, Peelman L, Deforce D, Van Soom A.During maternal recognition of pregnancy (MRP), a conceptus-derived signal leads to the persistence of the corpus luteum and the maintenance of gestation. In the horse, the nature of this signal remains to be elucidated. Several studies have focused on the changes in gene expression during MRP, but little information exists at the protein level. The aim of this study was to identify the proteins at the embryo-maternal interface around signalling of MRP in the horse (day 13) by means of mass spectrometry. A distinct influence of pregnancy was established, with 119 proteins differentially expres...
Bradbery AN, Coverdale JA, Vernon KL, Leatherwood JL, Arnold CE, Dabareiner RA, Kahn MK, Millican AA, Welsh TH.Seventeen yearling Quarter Horses were used in a randomized complete block design for a 56-d trial to determine ability of dietary CLA to mitigate joint inflammation and alter cartilage turnover following an inflammatory insult. Horses were blocked by age, sex, and BW, and randomly assigned to dietary treatments consisting of commercial concentrate offered at 1% BW (as-fed) supplemented with either 1% soybean oil (CON; n = 6), 0.5% soybean oil and 0.5% CLA (LOW; n = 5; 55% purity; Lutalin, BASF Corp., Florham Park, NJ), or 1% CLA (HIGH; n = 6) top-dressed daily. Horses were fed individually ev...
Pedersen SK, Cribb AE, Read EK, French D, Banse HE.In equids, phenylbutazone at high doses induces gastric disease, primarily in the glandular portion of the stomach. However, the mechanism of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric disease in horses has yet to be determined. While phenylbutazone-associated ulceration is often attributed to a decrease in basal gastric prostaglandins, this has not been demonstrated in the horse. Twelve horses were randomly assigned to treatment (n = 6; 4.4 mg/kg phenylbutazone PO in 20 ml molasses q 12 hr for 7 days) or placebo (n = 6; 20 ml molasses PO q 12 hr for 7 days) groups....
Ferreira JC, Filho LFN, Boakari YL, Canesin HS, Thompson DL, Lima FS, Meira C.The aim of the current project was to characterize the luteal vascularity and the plasma concentrations of progesterone (P4), prolactin (PRL) and 13,14-dihydro-15-keto-PGF (PGFM) in mares with luteal disturbances during early and mid-diestrus. In Experiment 1, twenty-one mares were treated with 2 mL of 0.9% NaCl, or 1 mg Dinoprost, or 10 mg Dinoprost on day two after ovulation (Control-D2, 1/10PGF-D2 and PGF-D2 groups, respectively; n = 7 mares/group). In Experiment 2, similar treatments were performed eight days post-ovulation using a different cohort of 21 mares (Control-D8, 1/10PGF-D8 ...
Fernandes CB, Loux SC, Scoggin KE, Squires EL, Troedsson MH, Esteller-Vico A, Ball BA.The cervix is a dynamic structure that undergoes dramatic changes during the estrous cycle, pregnancy and parturition. It is well established that hormonal changes, including estrogens, progestogens and prostaglandins, regulate the expression of key proteins involved in cervical function. The arachidonic acid cascade is important in the remodeling and relaxation of the cervix in the days preceding parturition. Despite the complexity of this mechanism, regulation of cervical function has received little study in the mare. Therefore, the objective of this study was to compare the expression of e...
MacNicol JL, Lindinger MI, Pearson W.Exercise is a physiological stress resulting in reactive oxygen species and inflammatory mediators, the accumulation of which are thought to contribute to degenerative articular diseases. The horse is of particular interest in this regard as equine athletes are frequently exposed to repetitive bouts of high-intensity exercise. The purpose of this study was to provide a detailed description of the response of articular and systemic oxidative and inflammatory biomarkers following high-intensity, exhaustive exercise in horses. A group of horses (Ex) underwent repeated bouts of high-intensity exer...
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...
Galvão A, Valente L, Skarzynski DJ, Szóstek A, Piotrowska-Tomala K, Rebordão MR, Mateus L, Ferreira-Dias G.Regulation of immune-endocrine interactions in the equine endometrium is not fully understood. The aims of the present study were to: (1) investigate the presence of tumour necrosis factor alpha (TNF), interferon gamma (IFNG), Fas ligand (FASLG) and their receptors in the mare endometrium throughout the oestrous cycle; and (2) assess endometrial secretory function (prostaglandins), angiogenic activity and cell viability in response to TNF, oestradiol (E2), progesterone (P4) and oxytocin (OXT). Transcription of TNF and FASLG mRNA increased during the early and late luteal phase (LP), whereas IF...
von Rechenberg B, Guenther H, McIlwraith CW, Leutenegger C, Frisbie DD, Akens MK, Auer JA.To define the release of nitric oxide (NO), prostaglandin E2 (PGE2), and the neutral metalloproteinases (NMPs) in horses with subchondral cystic lesions (SCL) and to study bone resorption triggered by conditioned media of fibrous tissue of SCL in vitro. Methods: Equine explant cultures of fibrous tissue of SCL, and synovial membrane and articular cartilage of normal horses and horses affected with moderate and severe osteoarthritis were performed. NO, PGE2, and NMP concentrations of media samples were measured, and osteoclast formation and activation was studied in vitro. Methods: Experiment 1...
Kawcak CE, Frisbie DD, Trotter GW, McIlwraith CW, Gillette SM, Powers BE, Walton RM.To evaluate the effects of arthroscopic surgery, osteochondral fragmentation, and treatment with IV administered hyaluronate on histologic, histochemical, and biochemical measurements within the carpal joints of horses. Methods: 12 clinically normal horses, 2 to 7 years of age. Methods: Horses had an osteochondral fragment created at the distal aspect of the radiocarpal bone of 1 randomly chosen middle carpal joint to simulate osteochondral fragmentation. Horses were treated with 40 mg of hyaluronate or saline solution (placebo) intravenously once a week for 3 consecutive weeks (days 13, 20, a...
Petrov R, MacDonald MH, Tesch AM, Benton HP.To investigate the effect of adenosine kinase inhibition on interleukin (IL)-1beta- and lipopolysaccharide (LPS)-induced cartilage damage. Methods: Articular cartilage was obtained from the metacarpophalangeal joints of 10 young adult horses. Following a stabilization period, weighed cartilage explants were exposed to IL-1beta (10 ng/ml) or LPS (50 microg/ml) to induce cartilage degradation. To test the potential protective effects of adenosine, these explants were simultaneously exposed to adenosine (100 microM), the adenosine kinase inhibitor 5'iodotubercidin (ITU, 1 microM) or to both adeno...
Piotrowska-Tomala KK, Jonczyk AW, Skarzynski DJ, Szóstek-Mioduchowska AZ.Prostaglandins (PGs) play crucial roles in the regulation of the oestrus cycle and establishment of pregnancy in animals. Luteinizing hormone (LH) and ovarian steroids are involved in regulating endometrial PG production in many species. Their effects on PG production and associated pathways in the mare myometrium and endometrium are the subjects of our interest. This study aimed to evaluate the specific effects of LH and ovarian steroids on equine myometrial and endometrial tissues on (i) PGE and PGF secretion and (ii) transcription of genes encoding specific enzymes responsible for PG synthe...
Bryant CE, Ouellette A, Lohmann K, Vandenplas M, Moore JN, Maskell DJ, Farnfield BA.Sepsis and endotoxaemia are important causes of morbidity and mortality in humans. Research on sepsis focuses on rodent models most of which are poorly responsive to lipopolysaccharide (LPS), and thus do not mimic very well the high sensitivity of humans. Therefore, there is a need to develop more clinically relevant models. Horses suffer from a similar endotoxaemic syndrome to humans with high morbidity and mortality. LPS analogues that act as antagonists at Toll-like receptor 4 (TLR4) are being developed as novel treatments for endotoxaemia. Due to differences in recognition of ligands by TL...
Byron CR, Stewart MC, Stewart AA, Pondenis HC.To evaluate the effects of glucosamine on equine articular chondrocytes and synoviocytes at concentrations clinically relevant to serum and synovial fluid concentrations. Methods: Articular cartilage and synovium with normal gross appearance from metacarpophalangeal and metatarsophalangeal joints of 8 horses (1 to 10 years of age). Methods: In vitro chondrocyte and synoviocyte cell cultures from 8 horses were treated with glucosamine (0.1 to 20 microg/mL) with or without interleukin-1 (IL-1; 10 ng/mL) for 48 hours. Negative control cultures received no glucosamine or IL-1, and positive control...
Ibrahim S, Szóstek-Mioduchowska A, Skarzynski D.Bacterial infections of the genital tract are the major cause of reproductive failure in the mares. MiRNAs are important regulators of gene expression, mostly through transcriptional and translational regression. We hypothesized that LPS induced aberrant expression of miRNAs and their targets, which are involved in regulation of uterine homeostasis. Three groups of primary endometrial epithelial and stromal cells, and endometrial tissue explants were cultured. The 1 group was kept as control, while the 2 and 3 groups were challenged with low (0.5 μg/mL) or high (3.0 μg/mL) doses of Lipop...
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...
Atli MO, Kurar E, Kayis SA, Aslan S, Semacan A, Celik S, Guzeloglu A.The aim was to evaluate expression of genes involved in the biosynthesis of prostaglandins (PTG), Prostaglandin H Synthase-1 (PTGS1) and PTGS2, PGF synthase (PTGFS), and PGE synthase (PTGES), PGF receptor (PTGFR), PGE receptors (PTGER2 and PTGER4), prostaglandin transporter (SLCO2A1) and hydroxyprostaglandin dehydrogenase-15 (HPGD). Endometrial biopsies were obtained from mares on day of ovulation (d0, n=4), late diestrus (LD, n=4), early luteolysis (EL, n=4) and after luteolysis (AL, n=4) during the cycle. Stages of the cycle were confirmed by plasma progesterone concentrations measured daily...
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...
Hammond RA, Hannon R, Frean SP, Armstrong SJ, Flower RJ, Bryant CE.To determine the amount of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) enzymes induced in vitro in equine alveolar macrophages in response to lipopolysaccharide (LPS). Sample Population-Alveolar macrophages obtained from 12 horses. Methods: Alveolar macrophages were collected by bronchoalveolar lavage from 12 horses and incubated for 6 hours with LPS (0.001 to 10 microg/ml) or vehicle. Total RNA was extracted and purified. After first-strand cDNA synthesis, mRNA induction was measured, using a polymerase chain reaction (PCR) technique for COX-2, iNOS, and glyceraldehyde...
Kirker-Head CA, Chandna VK, Agarwal RK, Morris EA, Tidwell A, O'Callaghan MW, Rand W, Kumar MS.To correlate substance P content of synovial fluid with prostaglandin E2 content, radiographic evidence of joint abnormality, and anatomic location of the joint for normal and osteoarthritic joints of horses. Methods: Synovial fluid from 46 normal joints in 21 horses and 16 osteoarthritic joints in 10 horses. Methods: Normal and osteoarthritic joints were identified by clinical and radiographic examination, by response to nerve blocks, during scintigraphy or surgery, or by clinicopathologic evaluation. Substance P and prostaglandin E2 contents of synovial fluid were determined by radioimmunoas...
Sharp DC, Thatcher MJ, Salute ME, Fuchs AR.The effect of transcervical endometrial biopsy on the concentrations of plasma immunoreactive oxytocin and 15-keto-13,14-dihydro-prostaglandin F2 alpha (PGFM) was studied in 18 pony mares on days 8, 12 and 14 after ovulation, days 12 and 14 of early pregnancy and at oestrus. Five biopsy specimens were taken within 15 min and consecutive specimens from each mare were pooled two (A) and three (B) together for measurement of the number of oxytocin receptors. Blood samples were collected at intervals of 5 min for 15 min beginning just before the initial biopsy. Biopsy procedure elicited prompt oxy...
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, ...
Pedersen SK, Cribb AE, Read EK, French D, Banse HE.In equids, phenylbutazone at high doses induces gastric disease, primarily in the glandular portion of the stomach. However, the mechanism of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric disease in horses has yet to be determined. While phenylbutazone-associated ulceration is often attributed to a decrease in basal gastric prostaglandins, this has not been demonstrated in the horse. Twelve horses were randomly assigned to treatment (n = 6; 4.4 mg/kg phenylbutazone PO in 20 ml molasses q 12 hr for 7 days) or placebo (n = 6; 20 ml molasses PO q 12 hr for 7 days) groups....
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, ...
de Grauw JC, Brama PA, Wiemer P, Brommer H, van de Lest CH, van Weeren PR.To assess whether reported alterations in metabolism of cartilage matrix in young (0 to 24 months old) horses with osteochondritis dissecans (OCD) may also be found in older (24 to 48 months old) horses with clinical signs of OCD and to investigate the role of eicosanoids in initiating these clinical signs. Methods: Synovial fluid was collected from 38 tarsocrural joints of 24 warmblood horses with (22 joints of 16 horses) or without (16 joints of 8 horses) clinical signs and a radiographic diagnosis of OCD of the distal intermediate ridge of the tibia. Methods: Turnover of type II collagen wa...
Nash D, Lane E, Herath S, Sheldon IM.Endometritis after insemination is ubiquitous in the horse and is associated with semen and/or bacteria in the uterus. In up to 40% of horses, inflammation persists causing infertility. An endometrial explant culture was developed to study uterine secretion of prostaglandin F(2alpha) (PGF(2alpha)) in response to physiological and pathological challenge. Methods: Uteri were collected from mares, the endometrium dissected and explants from the uterine body or horn cultured in William's or RPMI medium. The response of explants to oxytocin, semen or bacteria compared to untreated tissue was tested...
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...
