misoprostol and Edema

Misoprostol, a synthetic PGE1, is becoming a common therapy for mares with suspected uterine tube obstruction. Recently, there have been concerns that uterine administration of misoprostol induces exacerbated uterine inflammation; however, this has not been critically evaluated. This study aimed to assess the inflammatory response and potential systemic reactions after uterine administration of misoprostol, either during prebreeding or immediately after postembryo flushing. Privately owned embryo donor mares (n = 11) were randomly assigned in a crossover design to receive misoprostol (3 mL +200 µg) or sham (3 mL of lactate Ringer's solution) infusions, bilaterally deposited via deep-horn, at least 72 hours prebreeding (experiment 1) or immediately after embryo flushing (experiment 2). Each mare had one cycle for misoprostol and sham in both experiments and a breeding cycle (no sham or misoprostol) between experiments. Uterine edema, fluid accumulation, and the number of uterine PMN were assessed before each infusion and then daily for 72 hours. Uterine lavage was performed the day after each infusion across groups and experiments. Ovulation was hastened with a GnRH agonist and confirmed at 24 hour-intervals. Mares were bred with semen from one of six stallions per owner's choice. Embryo flushing was performed 8 to 9 days postovulation. In either experiment, misoprostol did not affect uterine edema or fluid accumulation (P > .05). However, both the sham and misoprostol infusions increased the number of PMN up to 48 hours postinfusion in both experiments. Embryo recoveries were similar between sham (45%, 5/11) and misoprostol cycles in experiments 1 (45%, 5/11; P > .05) and 2 (sham, 68%, 7/11; misoprostol, 45%, 5/11; P > .05). In conclusion, misoprostol did not induce exacerbated uterine inflammation in mares or systemic adverse reactions when infused prebreeding or immediately after embryo flushing.

Topics: Alprostadil; Animals; Edema; Female; Gonadotropin-Releasing Hormone; Horse Diseases; Horses; Inflammation; Lactates; Male; Misoprostol; Ringer's Solution; Uterine Diseases

Verbena officinalis L. is used in folk medicine for the treatment of inflammatory disorders, skin burns, abrasions, and gastric diseases. Extracts obtained with different solvents (methanol, VoME; enriched flavonoids, VoEF; supercritical CO2, VoCO2) were evaluated for anti-inflammatory, gastroprotective and cicatrizing activities. Additionally, the antioxidant capacity was determined in vitro. In order to confirm the activities investigated, histological observations were performed. All extracts induce a remarkable anti-inflammatory activity. The gastric damage is significantly reduced by all extracts administered, whereby the most pronounced protection is observed for the VoCO2 and VoEF extracts. Finally, a wound healing effect is obtained particularly by the CO2 extract, suggesting the presence of some lipophilic active principles. Histological evidence confirms the results evaluated with the animal procedures. The results obtained after oral administration of V. officinalis extracts are also in agreement with the antioxidant capacity evaluated in vitro, confirming the relationship between pharmacological activities and antiradical efficacy.

Topics: Animals; Anti-Ulcer Agents; Antioxidants; Carrageenan; Cicatrix; Edema; Male; Misoprostol; Phytotherapy; Plant Components, Aerial; Plant Extracts; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Verbena; Wound Healing

Recently, Th17 cells, a new subset of CD4+ T cells, emerged as major players in inflammation/autoimmunity. Maintenance of the Th17 phenotype requires interleukin-23 (IL-23), whereas the Th1-promoting cytokine IL-12p70 exerts a negative effect on Th17 cell differentiation. The lipid mediator prostaglandin E(2) (PGE(2)) acts primarily as a proinflammatory agent in autoimmune conditions, through mechanisms that remain to be elucidated. The aim of this study was to investigate whether PGE(2) released in inflammatory foci activates resident dendritic cells (DCs) to express IL-23 (at the expense of IL-12) and IL-6, resulting in a shift toward Th17 cell responses.. The effect of PGE(2) on IL-23 production by DCs and subsequent induction of T cell-derived IL-17 was assessed in vitro and in vivo. The effect of the stable PGE analog misoprostol was evaluated in a murine model of rheumatoid arthritis, in conjunction with IL-23 and IL-17 expression in affected joints and draining lymph nodes.. In vivo administration of PGE(2) induced IL-23-dependent IL-17 production. Administration of misoprostol exacerbated collagen-induced arthritis (CIA). CIA exacerbation was associated with increased levels of IL-23p19/p40 messenger RNA and reduced expression of IL-12p35, and with increased levels of the proinflammatory cytokines IL-17, IL-1beta, IL-6, and tumor necrosis factor in the affected joint. Following ex vivo restimulation, draining lymph node cells from misoprostol-treated mice secreted higher levels of IL-17 and lower levels of interferon-gamma.. Our results indicate that PGE(2) enhances DC-derived IL-6 production and induces a shift in the IL-23/IL-12 balance in favor of IL-23, resulting in increased IL-17 production, presumably through the amplification of self-reactive Th17 cells.

Topics: Animals; Arthritis, Experimental; Cells, Cultured; Cytokines; Dendritic Cells; Dinoprostone; Edema; Gene Expression; Hindlimb; Interleukin-17; Interleukin-23; Lymph Nodes; Male; Mice; Mice, Inbred BALB C; Misoprostol; RNA, Messenger; Spleen; T-Lymphocytes; Toe Joint

This study has evaluated the anti-inflammatory and analgesic responses of etoricoxib, a selective COX-2 non-steroidal anti-inflammatory drug combined with misoprostol in pre-clinical assays. Groups of animals (mice and rats) were subjected to rat's paw edema induced by carrageenan, and writhing and formalin tests in mice. Treatment with etoricoxib, misoprostol, and etoricoxib combined with misoprostol inhibited the inflammation process by 35 %, 30 %, and 61 %, respectively in the rat paw edema induced by carrageenan with the greatest effects being obtained in the group treated with etoricoxib combined to misoprostol. In the writhing test, etoricoxib inhibited the number of writhes by 33 %, and by 27 % when combined with misoprostol. In the first phase of the formalin test (nociceptive), treatment with the combination of etoricoxib and misoprostol inhibited significantly this process by 45 %, while in the second phase (inflammatory), etoricoxib inhibited this by 97 %, the etoricoxib + misoprostol inhibited this by 78 %, respectively. The responses observed have demonstrated that the combination of etoricoxib and misoprostol increased the anti-inflammatory response, but it did not show effect in the peripheral analgesic response.

Topics: Analysis of Variance; Animals; Anti-Ulcer Agents; Carrageenan; Cyclooxygenase 2 Inhibitors; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Edema; Etoricoxib; Male; Mice; Misoprostol; Pain; Pain Measurement; Pyridines; Rats; Rats, Wistar; Sulfones

In noninfected rats, challenge with allergen following local IgE sensitization induced a pleurisy marked by intense protein exudation that plateaued from 30 min to 4 h after challenge, reducing thereafter. Infection of rats with Angiostrongylus costaricensis induced a 5-fold increase in blood eosinophil numbers by 25 days postinfection, whereas the numbers of eosinophils in the pleural cavity ranged from normal to a weak increase. In infected rats, identically sensitized, challenge with Ag induced a much shorter duration of pleural edema with complete resolution by 4 h, but no change in the early edema response. In parallel, infection increased the number of eosinophils recovered from the pleural cavity at 4 h, but not at 30 min, following allergen challenge. Pretreatment with IL-5 (100 IU/kg, i.v.) also increased eosinophil numbers in blood and, after allergen challenge, shortened the duration of the pleural edema and increased pleural eosinophil numbers. There were increases in the levels of both PGE2 and lipoxin A4 (LXA4) in pleural exudate. Selective cyclooxygenase (COX)-2 inhibitors, NS-398, meloxicam, and SC-236, did not alter pleural eosinophilia, but reversed the curtailment of the edema in either infected or IL-5-pretreated rats. Pretreatment of noninfected animals with the PGE analogue, misoprostol, or two stable LXA4 analogues did not alter the magnitude of pleural exudation response, but clearly shortened its duration. These results indicate that the early resolution of allergic pleural edema observed during A. costaricensis infection coincided with a selective local eosinophilia and seemed to be mediated by COX-2-derived PGE2 and LXA4.

Topics: Administration, Oral; Angiostrongylus; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens, Helminth; Corticosterone; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Edema; Eosinophilia; Exudates and Transudates; Female; Hydroxyeicosatetraenoic Acids; Hypersensitivity; Injections, Intraperitoneal; Injections, Intravenous; Interleukin-5; Isoenzymes; Kinetics; Leukotriene C4; Lipoxins; Male; Misoprostol; Pleural Effusion; Pleurisy; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Strongylida Infections

Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the central nervous system (CNS). It is an animal model of post-infectious encephalomyelitis and multiple sclerosis (MS). Acute EAE is mediated by macrophages and by T helper 1 (Th1) lymphocytes directed against brain antigens. Inflammation in EAE could potentially be modified by prostaglandins (PG) secreted by blood monocytes (Mo) and brain glial cells. PGE elevates cAMP, which inhibits Mo function and selectively blocks secretion of cytokines by Th1 cells. In the present study, we found that a long-acting PGE1 analogue (LAPGE) inhibited clinical and histological EAE. Indomethacin (INDO) also suppressed active EAE. The combination of INDO plus LAPGE inhibited disease further, possibly by allowing LAPGE to function unopposed by immunostimulatory PG. EAE was suppressed when these agents were administered from the time of immunization or from the onset of clinical disease. The combination of INDO plus LAPGE also inhibited delayed-type hypersensitivity (DTH) reactions to myelin basic protein (MBP), and diminished in vitro lymphocyte responses to mitogens and MBP. PGE analogues and modifiers of arachidonate metabolism block autoimmune responses to brain antigens in vitro and in vivo, and may ameliorate inflammatory and autoimmune diseases of the brain and other organs.

Topics: Alprostadil; Animals; Arachidonic Acid; Drug Combinations; Edema; Encephalomyelitis, Autoimmune, Experimental; Female; Hypersensitivity, Delayed; Indomethacin; Lymphocyte Activation; Misoprostol; Myelin Basic Protein; Prostaglandins; Rats; Rats, Inbred Lew

The effects of prostaglandin E1 (PGE1) and certain PGE-analogs on edema formation were investigated in mouse and rat skin. In the mouse, intradermal administration of both zymosan-activated serum (ZAS) (5-50% per site) and platelet-activating factor (PAF) (0.1-5.0 nmol/site) caused dose-related increases in edema formation. PGE1 (0.003-3.0 nmol/site) caused a dose-related inhibition of the edema response to ZAS, whereas a dose of 0.3 nmol potentiated the edema response to PAF. Sulprostone, which is selective for EP1 and EP3 PGE-receptors, produced a potent inhibition of the edema responses to both ZAS (80%) and PAF (60%). Misoprostol, which is selective for both EP2- and EP3-receptors, inhibited the edema response to ZAS (> 40%) but had no effect on the response to PAF. Treatment of mice with the thromboxane A2-receptor antagonist GR32191B did not modify the anti-inflammatory activity of PGE1 or sulprostone. In the rat skin model, PGE1 produced only potentiation of the responses to both ZAS and PAF. However, sulprostone displayed significant inhibitory effects on the edema responses to both stimuli (40-50%). From these data we propose that the anti-inflammatory activity of PGE1 and of the two analogs sulprostone and misoprostol may be mediated via activation of the contractile EP3-receptor. Differences in the responses to prostanoids from one species to another may reflect differences in the relative densities of receptor subtypes mediating opposite effects.

Topics: Alprostadil; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood; Dinoprostone; Edema; Male; Mice; Misoprostol; Platelet Activating Factor; Rats; Rats, Wistar; Receptors, Prostaglandin E; Skin; Zymosan

This study was performed to assess the effects of misoprostol, a synthetic prostaglandin E1 analog, on cerulein-induced pancreatitis. Per group of 10 each, male Wistar rats received either cerulein (2.5 micrograms/kg/h subcutaneously), cerulein and misoprostol (500 micrograms/kg intraperitoneally at 0 and 4 h), or saline. Rats were killed 6 h after the first injection. Misoprostol treatment significantly reduced interstitial edema and acinar cell lesions induced by hyperstimulation. Pancreatic amylase and chymotrypsin contents were increased by cerulein and returned towards control levels in the misoprostol-treated group. The lysosomal volume density and the pancreatic beta-D-glucuronidase activity were significantly increased after hyperstimulation. The two parameters were significantly reduced by misoprostol. A protective effect of misoprostol against lesions induced by cerulein hyperstimulation would be a consequence of a lysosomal stabilizating effect.

Topics: Acid Phosphatase; Acute Disease; Alprostadil; Amylases; Animals; Ceruletide; Chymotrypsin; Edema; Glucuronidase; Male; Microscopy, Electron; Misoprostol; Organ Size; Pancreatic Diseases; Pancreatitis; Prostaglandins E, Synthetic; Rats; Rats, Inbred Strains