Topic:Anti-inflammatory
Anti-inflammatory agents are substances used to reduce inflammation in horses, often employed in the management of various equine conditions. These agents can be categorized into non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, among others. NSAIDs, such as phenylbutazone and flunixin meglumine, work by inhibiting cyclooxygenase enzymes, which play a role in the inflammatory process. Corticosteroids, like dexamethasone, modulate the immune response and reduce inflammation through their effects on gene expression. The use of anti-inflammatory agents is common in equine veterinary practice to alleviate pain and improve the quality of life in horses suffering from musculoskeletal disorders, colic, and other inflammatory conditions. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacology, efficacy, and safety of anti-inflammatory agents in equine medicine.
Pharmacokinetics of intravenous flumetasone and effects on plasma hydrocortisone concentrations and inflammatory mediators in the horse. Flumetasone is a potent corticosteroid reportedly used in horses to decrease inflammation associated with strenuous exercise. There are currently no reports describing the use of this drug in horses. Objective: To describe the pharmacokinetics and effects on cortisol and eicosanoid concentrations, following administration of flumetasone to exercised horses. Methods: Parallel design. Methods: Twelve exercised horses received a single i.v. administration of 5 mg of flumetasone. Blood and urine samples were collected before and for 72 h post-drug administration for determination of flumetasone an...
In vitro effects of three equimolar concentrations of methylprednisolone acetate, triamcinolone acetonide, and isoflupredone acetate on equine articular tissue cocultures in an inflammatory environment. OBJECTIVE To compare the effects of 3 equimolar concentrations of methylprednisolone acetate (MPA), triamcinolone acetonide (TA), and isoflupredone acetate (IPA) on equine articular tissue cocultures in an inflammatory environment. SAMPLE Synovial and osteochondral explants from the femoropatellar joints of 6 equine cadavers (age, 2 to 11 years) without evidence of musculoskeletal disease. PROCEDURES From each cadaver, synovial and osteochondral explants were harvested from 1 femoropatellar joint to create cocultures. Cocultures were incubated for 96 hours with (positive control) or without (n...
A rapid and sensitive method for the quantitative analysis of ibuprofen and its metabolites in equine urine samples by gas chromatography with tandem mass spectrometry. Ibuprofen is widely used in human and veterinary medicine for the treatment of chronic pain as well as rheumatic and musculoskeletal disorders. However, the analgesic and anti-inflammatory properties of Ibuprofen have contributed to frequent drug abuse in equestrian sports. A sensitive and rapid gas chromatography with tandem mass spectrometry based method with a simple liquid-liquid extraction and derivatization requiring 200 μL volume of sample and 2 mL of extraction solvent for the simultaneous determination of ibuprofen and its metabolites was developed. The proposed procedure was optim...
Differential effects of selective and non-selective cyclooxygenase inhibitors on fecal microbiota in adult horses. Non-steroidal anti-inflammatory drugs (NSAIDs) are routinely used in both veterinary and human medicine. Gastrointestinal injury is a frequent adverse event associated with NSAID use and evidence suggests that NSAIDs induce gastrointestinal microbial imbalance (i.e., dysbiosis) in both animals and people. It is unknown, however, whether cyclooxygenase (COX)-2-selective NSAIDs induce dysbiosis, or if this phenomenon occurs in horses administered any class of NSAIDs. Therefore, our objectives were to determine whether the composition and diversity of the fecal microbiota of adult horses were alt...
Effect of selective versus nonselective cyclooxygenase inhibitors on gastric ulceration scores and intestinal inflammation in horses. To determine whether a cyclooxygenase (COX)-2 selective nonsteroidal anti-inflammatory drug (NSAID) would reduce gastric ulceration and gastrointestinal (GI) inflammation compared with a non-COX selective NSAID. Methods: Randomized block design. Methods: Twenty-five healthy adult horses. Methods: Horses were randomly assigned to receive placebo (n = 5), phenylbutazone (n = 10), or firocoxib (n = 10) administered daily for 10 days. Gastroscopy was performed on days 0 and 10, and both squamous and glandular ulcers were scored according to established scoring criteria. Fecal samples w...
Rifaximin anti-inflammatory activity on bovine endometrium primary cell cultures: a preliminary study. Rifaximin is an unabsorbed oral antibiotic showing anti-inflammatory properties in human pathologies like irritable bowel syndrome and inflammatory bowel disease. In veterinary medicine, rifaximin is primarily used in the treatment of dermatological diseases in all animal species, in therapy and prophylaxis of mastitis in cows and in the treatment of endometritis in cattle and horses. The aim of this preliminary study was to evaluate the anti-inflammatory properties of rifaximin on primary cell cultures from bovine endometrium in which inflammatory response was induced by Lipopolysaccaride (LP...
Intra-articular delivery of a nanocomplex comprising salmon calcitonin, hyaluronic acid, and chitosan using an equine model of joint inflammation. Polyelectrolyte nanoparticle constructs (NPs) comprising salmon calcitonin (sCT), chitosan (CS), and hyaluronic acid (HA) were previously established as having anti-inflammatory potential when injected via the intra-articular (i.a.) route to a mouse model. We attempted to translate the formulation to a large animal model, the lipopolysaccharide (LPS)-stimulated equine model of joint inflammation. The aim was to manufacture under aseptic conditions to produce sterile pyrogen-free NPs, to confirm physicochemical characteristics, and to test toxicity and efficacy in a pilot study. NP dispersions ...
Degradation, Intra-Articular Biocompatibility, Drug Release, and Bioactivity of Tacrolimus-Loaded Poly(d-l-lactide-PEG)-b-poly(l-lactide) Multiblock Copolymer-Based Monospheres. The aim of this study was to develop a formulation with a sustained intra-articular release of the anti-inflammatory drug tacrolimus. Drug release kinetics from the prepared tacrolimus loaded monodisperse biodegradable microspheres based on poly(d-l-lactide-PEG)--poly(l-lactide) multiblock copolymers were tunable by changing polymer composition, particularly hydrophobic-hydrophilic block ratio. The monospheres were 30 μm and released the drug, depending on the formulation, in 7 to >42 days. The formulation exhibiting sustained release for 1 month was selected for further in vivo evaluation...
Greenshell™ Mussels: A Review of Veterinary Trials and Future Research Directions. The therapeutic benefits of Greenshell™ mussel (GSM; Perna canaliculus) preparations have been studied using in vitro test systems, animal models, and human clinical trials focusing mainly on anti-inflammatory and anti-arthritic effects. Activity is thought to be linked to key active ingredients that include omega-3 polyunsaturated fatty acids, a variety of carotenoids and other bioactive compounds. In this paper, we review the studies that have been undertaken in dogs, cats, and horses, and outline new research directions in shellfish breeding and high-value nutrition research programmes ta...
Detection and pharmacokinetics of grapiprant following oral administration to exercised Thoroughbred horses. Traditional therapeutic options for the treatment of lameness associated with inflammation in performance horses include administration of cyclooxygenase enzyme inhibiting non-steroidal anti-inflammatory drugs (NSAID). As long-term use of these drugs can adversely impact the health of the horse, anti-inflammatories with a more favorable safety profile are warranted. Grapiprant is a newly approved non-cyclooxygenase inhibiting NSAID that has demonstrated efficacy and safety in other species and which may be a valuable alternative to traditional NSAIDs used in the horse. The objectives of the cu...
Analysis of loxoprofen in tablets, patches, and equine urine as tert-butyldimethylsilyl derivative by gas chromatography-mass spectrometry. Loxoprofen is a non-steroidal anti-inflammatory drug of the 2-arylpropionic acid type, which has used to treat musculoskeletal disorders in the horse racing industry. However, it has also used illicitly to mask clinical signs of inflammation and pain in racehorses. Thus, its accurate analysis has become an important issue in horse doping laboratories. In this study, an analytical method of loxoprofen was developed as tert-butyldimethylsilyl (TBDMS) derivative by gas chromatography-mass spectrometry (GC-MS). Characteristic fragment ions of [M-15], [M-57], and [M-139] permitted the accurate and ...
MicroRNAs of Equine Amniotic Mesenchymal Cell-derived Microvesicles and Their Involvement in Anti-inflammatory Processes. Cell-derived microvesicles (MVs) are a recently discovered mechanism of cell-to-cell communication. Our previous data show that MVs secreted by equine amniotic mesenchymal-derived cells (AMCs) are involved in downregulation of proinflammatory genes in lipopolysaccharide-stressed equine tendon and endometrial cells. The aim of the present study was to evaluate whether AMC-MVs contain selected microRNAs (miRNAs) involved in inflammation. Two pools of cells, derived from 3 amniotic membranes each, and their respective MVs were collected. Small RNAs were extracted and deep sequenced, followed by m...
Antiarrhythmic Effects of Combining Dofetilide and Ranolazine in a Model of Acutely Induced Atrial Fibrillation in Horses. Antiarrhythmic compounds against atrial fibrillation (AF) often have reduced efficacy and may display cardiac and/or noncardiac toxicity. Efficacy can be improved by combining 2 compounds with distinct mechanisms, and it may be possible to use lower doses of each compound, thereby reducing the likelihood of adverse side effects. The purpose of this study was to investigate whether the effective doses of dofetilide and ranolazine can be reduced if the drugs are combined. Dofetilide, ranolazine, and a combination of these were administered in 4 incremental dosing regimens to horses with acutely ...
Pharmacokinetics and antinociceptive effects of the soluble epoxide hydrolase inhibitor t-TUCB in horses with experimentally induced radiocarpal synovitis. This study determined the pharmacokinetics, antinociceptive, and anti-inflammatory effects of the soluble epoxide hydrolase (sEH) inhibitor t-TUCB (trans-4-{4-[3-(4-Trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid) in horses with lipopolysaccharide (LPS)-induced radiocarpal synovitis. A total of seven adult healthy mares (n = 4-6/treatment) were administered 3 μg LPS into one radiocarpal joint and t-TUCB intravenously (i.v.) at 0 (control), 0.03, 0.1, 0.3, and 1 mg/kg in a blinded, randomized, crossover design with at least 3 weeks washout between. Two investigators independe...
Postoperative pharmacokinetics of meloxicam in horses after surgery for colic syndrome. NSAIDs are often used in horses with colic syndrome during the postoperative period, due to their ability to contrast endotoxemia and to promote an analgesic and anti-inflammatory effect. As the pharmacokinetics of a drug are often modified in unhealthy animals compared to healthy subjects, the aim of this study was to evaluate the pharmacokinetic profile of meloxicam after i.v. administration in horses undergoing laparotomy for colic syndrome. Eight horses received 0.6 mg/kg of meloxicam i.v. towards the end of surgery. Blood samples were taken at scheduled time points during the following 2...
Inhibition of microsomal prostaglandin E-synthase-1 (mPGES-1) selectively suppresses PGE2 in an in vitro equine inflammation model. 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...
Misoprostol Inhibits Lipopolysaccharide-Induced Pro-inflammatory Cytokine Production by Equine Leukocytes. Pro-inflammatory cytokines including tumor necrosis factor α (TNFα), IL-1β, IL-6, and IL-8 are potent immune mediators that exacerbate multiple equine diseases such as sepsis and laminitis. Unfortunately, safe and effective cytokine-targeting therapies are lacking in horses; therefore, novel mechanisms of inhibiting cytokine production are critically needed. One potential mechanism for inhibiting cytokine synthesis is elevation of intracellular cyclic AMP (cAMP). In human leukocytes, intracellular cAMP production is induced by activation of E-prostanoid (EP) receptors 2 and 4. These recepto...
Misoprostol Inhibits Equine Neutrophil Adhesion, Migration, and Respiratory Burst in an In Vitro Model of Inflammation. In many equine inflammatory disease states, neutrophil activities, such as adhesion, migration, and reactive oxygen species (ROS) production become dysregulated. Dysregulated neutrophil activation causes tissue damage in horses with asthma, colitis, laminitis, and gastric glandular disease. Non-steroidal anti-inflammatory drugs do not adequately inhibit neutrophil inflammatory functions and can lead to dangerous adverse effects. Therefore, novel therapies that target mechanisms of neutrophil-mediated tissue damage are needed. One potential neutrophil-targeting therapeutic is the PGE1 analog, m...
Ultrastructural characteristics and immune profile of equine MSCs from fetal adnexa. Both in human and equine species, mesenchymal stem cells (MSCs) from amniotic membrane (AM) and Wharton's jelly (WJ), may be particularly useful for immediate use or in later stages of life, after cryopreservation in cell bank. The aim of this study was to compare equine AM- and WJ-MSCs features that may be relevant for their clinical employment. MSCs were more easily isolated from WJ, even if MSCs derived from AM exhibited more rapid proliferation ( < 0.05). Osteogenic and chondrogenic differentiation were more prominent in MSCs derived from WJ. This is also suggested by the lower adh...
Determination of vitacoxib, a novel COX-2 inhibitor, in equine plasma using UPLC-MS/MS detection: Development and validation of new methodology. Vitacoxib is an imidazole derivative and the novel COX-2 selective inhibitor to be marketed for veterinary use as nonsteroidal anti-inflammatory drugs. No analytical assay to quantify vitacoxib in equine plasma samples has been published to date. In the current study, we aim to develop and validate a brief, quick and sensitive UPLC-MS/MS method for quantification of vitacoxib in equine plasma samples. Plasma samples were precipitated with methyl tert-butyl ether. The Phenomenex column (Kinetex 50×2.1mm i.d. particle size=2.6μm, C18, 100Å) at 25°C was used in chromatographic separation with...
Proinflammatory and Anabolic Gene Expression Effects of Platelet-Rich Gel Supernatants on Equine Synovial Membrane Explants Challenged with Lipopolysaccharide. Platelet-rich plasma (PRP) preparations are used in horses with osteoarthritis (OA). However, some controversies remain regarding the ideal concentration of platelets and leukocytes to produce an adequate anti-inflammatory and anabolic response in the synovial membrane. The aims of this study were to study the influence of leukoconcentrated platelet-rich gel (Lc-PRG) and leukoreduced platelet-rich gel (Lr-PRG) supernatants on the quantitative expression of some proinflammatory and anabolic genes in equine synovial membrane explants (SMEs) challenged with lipopolysaccharide (LPS). SMEs from six...
In vitro anti-LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses. 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...
Update on the use of cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs in horses. Nonsteroidal anti-inflammatory drugs work through inhibition of cyclooxygenase (COX) and are highly effective for the treatment of pain and inflammation in horses. There are 2 clinically relevant isoforms of COX. Cyclooxygenase-1 is constitutively expressed and is considered important for a variety of physiologic functions, including gastrointestinal homeostasis. Thus, NSAIDs that selectively inhibit COX-2 while sparing COX-1 may be associated with a lower incidence of adverse gastrointestinal effects. Various formulations of firocoxib, a COX-2-selective NSAID, labeled for use in horses are av...
Retinoic acid-mediated anti-inflammatory responses in equine immune cells stimulated by LPS and allogeneic mesenchymal stem cells. Retinoic acid (RA), an active metabolite of vitamin A, has shown potential therapeutic immunomodulatory properties. Allogeneic mesenchymal stem cells (MSCs)-based therapy is an effective approach to induce tissue healing and regeneration in many equine orthopedic conditions. However, MSCs-based therapies induced inflammatory responses in vivo. This study aimed to: 1. Determine the effect of RA cell culture treatment on inflammatory responses of lipopolysaccharides (LPS)- and allogeneic MSCs-stimulated peripheral blood mononuclear cells (PBMCs). 2. Determine the effect of RA on stimulated MSCs ...
Effects of hyaluronan alone or in combination with chondroitin sulfate and N-acetyl-d-glucosamine on lipopolysaccharide challenge-exposed equine fibroblast-like synovial cells. 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),...
Inhalation Therapy in Horses. This article discusses the benefits and limitations of inhalation therapy in horses. Inhalation drug therapy delivers the drug directly to the airways, thereby achieving maximal drug concentrations at the target site. Inhalation therapy has the additional advantage of decreasing systemic side effects. Inhalation therapy in horses is delivered by the use of nebulizers or pressured metered dose inhalers. It also requires the use of a muzzle or nasal mask in horses. Drugs most commonly delivered through inhalation drug therapy in horses include bronchodilators, antiinflammatories, and antimicrobi...
Nonsteroidal Anti-inflammatory Drug Use in Horses. Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective anti-inflammatory and analgesic agents and are arguably the most commonly used class of drugs in equine medicine. This article provides a brief review of the mechanism of action, therapeutic uses, pharmacokinetics, and adverse effects associated with their use in horses. The use of COX-2 selective NSAIDs in veterinary medicine has increased over the past several years and special emphasis is given to the use of these drugs in horses. A brief discussion of the use of NSAIDs in performance horses is also included.
Pharmacokinetics and in vitro efficacy of salicylic acid after oral administration of acetylsalicylic acid in horses. Although acetylsalicylic acid (ASA) is not frequently used as a therapeutic agent in horses, its metabolite SA is of special interest in equestrianism since it is a natural component of many plants used as horse feed. This led to the establishment of thresholds by horse sport organizations for SA in urine and plasma. The aim of this study was to investigate plasma and urine concentrations of salicylic acid (SA) after oral administration of three different single dosages (12.5 mg/kg, 25 mg/kg and 50 mg/kg) of acetylsalicylic acid (ASA) to eight horses in a cross-over designed study. Results:...
Anti-inflammatory drugs decrease infection of brain endothelial cells with EHV-1 in vitro. Equine herpesvirus-associated myeloencephalopathy is the result of endothelial cell infection of the spinal cord vasculature with equine herpesvirus-1 (EHV-1) during cell-associated viraemia. Endothelial cell infection requires contact between infected peripheral blood mononuclear and endothelial cells. Inflammation generated during viraemia likely upregulates adhesion molecule expression on both cell types increasing contact and facilitating endothelial cell infection. Objective: Evaluating the role of anti-inflammatory drugs in decreasing endothelial cell infection with EHV-1. Methods: In vi...
α-Lipoic Acid Potentiates the Anti-Inflammatory Activity of Avocado/Soybean Unsaponifiables in Chondrocyte Cultures. 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...