misoprostol and Inflammation

Gastrointestinal harm, known to occur with NSAIDs, is thought to be lower with NSAID and gastroprotective agent, and with inhibitors selective to cyclooxygenase-2 (coxibs) at usual plasma concentrations. We examine competing strategies for available evidence of reduced gastrointestinal bleeding in clinical trials and combine this evidence with evidence from clinical practice on whether the strategies work in the real world, whether guidance on appropriate prescribing is followed, and whether patients adhere to the strategies.. We used a series of systematic literature searches to find full publications of relevant studies for evidence about the efficacy of these different gastroprotection strategies in clinical trials, and for evidence that they worked and were adhered to in clinical practice--whether they were effective. We chose to use good quality systematic reviews and meta-analyses when they were available.. Evidence of efficacy of coxibs compared to NSAIDs for upper gastrointestinal bleeding was strong, with consistent reductions in events of about 50% in large randomised trials (34,460 patients), meta-analyses of randomised trials (52,474 patients), and large observational studies in clinical practice (3,093 bleeding events). Evidence on the efficacy of NSAID plus gastroprotection with acid suppressants (proton pump inhibitors, PPIs, and histamine antagonists, H2As) was based mainly on the surrogate measure of endoscopic ulcers. The limited information on damage to the bowel suggested that NSAID plus PPI was more damaging than coxibs. Eleven observational studies studied 1.6 million patients, of whom 911,000 were NSAID users, and showed that 76% (range 65% to 90%) of patients with at least one gastrointestinal risk factor received no prescription for gastroprotective agent with an NSAID. The exception was a cohort of US veterans with previous gastrointestinal bleeding, where 75% had gastroprotection with an NSAID. When gastroprotection was prescribed, it was often described as inadequate. A single study suggested that patient adherence to prescribed gastroprotection was low.. Evidence for efficacy of gastroprotection strategies with NSAIDs is limited. In clinical practice few patients who need gastroprotection get it, and those who get it may not take it. For coxibs, gastroprotection is inherent, although probably not complete.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Clinical Trials as Topic; Cyclooxygenase 2 Inhibitors; Drug Therapy, Combination; Gastrointestinal Hemorrhage; Gastrointestinal Tract; Histamine Antagonists; Humans; Inflammation; Meta-Analysis as Topic; Misoprostol; Patient Compliance; Practice Patterns, Physicians'; Proton Pumps; Treatment Outcome

Osteoarthritis (OA) is not a simple consequence of "wear and tear" or aging--the presence of cytokines suggests a role for inflammation. OA is polyarticular in most patients, with metabolic and differential risk factors for prevalence and severity. Odds ratios for the prevalence of OA according to formal education levels are similar to those seen for dysregulatory diseases such as hypertension, diabetes, and rheumatoid arthritis. Clinical survey data indicate significant patient preference for nonsteroidal anti-inflammatory drugs (NSAIDs) compared with acetaminophen. A recent crossover clinical trial indicated significantly greater efficacy of the NSAID, diclofenac/misoprostol, versus acetaminophen for most patients with OA.

Topics: Acetaminophen; Adult; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug Combinations; Humans; Inflammation; Middle Aged; Misoprostol; Osteoarthritis; Risk Factors; Socioeconomic Factors

Misoprostol, a prostaglandin E1 analogue, is currently licensed primarily to prevent non-steroidal anti-inflammatory drug-associated gastric and duodenal ulcers. Further work shows the drug prevents triggering of a variety of inflammatory processes and the release of tissue damaging cytokines and other mediators involved in conditions as diverse as asthma and osteoarthritis. Thus, misoprostol may help restore or maintain normal homeostasis and limit inhibitory effects on essential repair processes. Therapeutic implications include limitation of renal, hepatic, gastrointestinal and radiation-induced tissue injury and prevention of inflammatory and allergic disorders, including the late phase inflammatory response in asthma, either alone or in synergy with other agents.

Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Humans; Inflammation; Misoprostol; Mucous Membrane

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

The objective of the present study was to investigate the effect of vaginally and orally administered misoprostol on the local cervical inflammatory response.. Healthy women with a normal intrauterine pregnancy between 8 and 12 weeks of gestation presenting for an elective termination of pregnancy by vacuum aspiration were recruited into a cohort study with a control and a treatment group. In the treatment group, the women were randomized to misoprostol, 400 mug, given either orally or vaginally 3 h before surgery. Immunohistochemistry staining of CD45, CD68, MMP 8, MMP 9, TIMP 1 and TIMP 2 were assessed in cervical biopsies obtained directly prior to mechanical cervical dilatation and vacuum aspiration.. In the treatment group, there was a greater amount of CD45-positive cells in the subepithelium region of the cervix compared to the control group. The staining of CD68 was similar in both groups. The immunostaining of MMP 8 and MMP 9 was greater in the treatment group, while the expression of TIMP 1 and TIMP 2 did not differ between control and treatment groups.. Compared to untreated controls, treatment with misoprostol was associated with a greater expression of inflammatory cells. It could be hypothesized that administration of misoprostol mimics the cervical ripening at term pregnancy by a possible influx and activation of inflammatory cells, which increases MMP 8 and MMP 9 and thereby leads to the degradation of collagen and cervical softening.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Administration, Intravaginal; Administration, Oral; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Cervical Ripening; Female; Gestational Age; Humans; Immunohistochemistry; Inflammation; Leukocyte Common Antigens; Matrix Metalloproteinase 8; Matrix Metalloproteinase 9; Misoprostol; Pregnancy; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Vacuum Curettage

The effect of misoprostol, a synthetic analogue of prostaglandin E, on prostaglandin concentrations in synovial fluids was investigated in a randomised placebo controlled, double blind study. The synovial fluid concentrations of prostaglandin E1, 6-keto-prostaglandin F1 alpha, and thromboxane B2 were measured at the beginning and end of a 24 hour period in 25 patients with effusions of the knee joint. During this period the patients were treated with diclofenac (50 mg every eight hours) and either misoprostol (400 micrograms) or placebo every 12 hours. The concentrations of prostaglandin E and 6-keto-prostaglandin F1 alpha were not significantly altered during treatment. There was an unexpected significant reduction in thromboxane B2 concentrations in the group treated with misoprostol (within group analysis). Although the mean concentration with misoprostol was about half the mean concentration with placebo, this difference was not statistically significant in the between group analysis. These results indicate that misoprostol is unlikely to exert a proinflammatory effect or to interfere with the prostaglandin mediated effects of non-steroidal anti-inflammatory drugs. The significant decrease in thromboxane B2 concentrations in the misoprostol treated group suggests that misoprostol may exert an anti-inflammatory effect.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Aged, 80 and over; Alprostadil; Double-Blind Method; Humans; Inflammation; Knee Joint; Middle Aged; Misoprostol; Random Allocation; Synovial Fluid; Thromboxane B2

Heat stroke is a life-threatening disorder triggered by thermoregulatory failure. Hyperthermia-induced splanchnic hypoperfusion has been reported to induce intestinal barrier dysfunction and systemic immune response that ultimately cause multiple-organ failure and death. Intestinal goblet cells contribute greatly to the formation of mucus barrier, which hinders translocation of gut microorganisms. Studies have reported that misoprostol can not only alleviate ischemic injury but also protect GI mucosal layer. Therefore, we evaluated the effects of misoprostol on intestinal goblet cells after heat stress and on multiple-organ dysfunction in heat stroke rats.. Heat stress was established in the heating chamber and followed by misoprostol treatment. Changes in hemodynamics, organ function indices, inflammation, oxidative stress, and survival rate were analyzed. Furthermore, ilea and LS174T cells were used to examine intestinal functions.. Heat stress caused dysfunction of intestinal goblet cells and damage to ilea by increasing oxidative stress and apoptosis. Increased nitrosative stress and inflammation accompanied by hypotension, hypoperfusion, tachycardia, multiple-organ dysfunction, and death were observed in the heat stroke rat model. Treatment of LS174T cells with misoprostol not only decreased oxidative stress and apoptosis but also reduced cytotoxicity caused by heat stress. Moreover, misoprostol prevented disruption of the enteric barrier, multiple-organ injury, and death in rats with heat stroke.. This study indicates that misoprostol could alleviate intestinal damage and organ injury caused by heat stress and be a potential therapy for heat-related illnesses.

Topics: Alprostadil; Animals; Goblet Cells; Heat Stroke; Heat-Shock Response; Inflammation; Intestinal Mucosa; Misoprostol; Multiple Organ Failure; Rats

Intracerebral hemorrhage (ICH) is a devastating form of stroke. Misoprostol, a synthetic prostaglandin E1 (PGE1) analog and PGE2 receptor agonist, has shown protection against cerebral ischemia. In this study, we tested the efficacy of misoprostol in the 12-month-old mice subjected to 1 of 2 complementary ICH models, the collagenase model (primary study) and blood model (secondary study, performed in an independent laboratory). We also investigated its potential mechanism of action. Misoprostol posttreatment decreased brain lesion volume, edema, and brain atrophy and improved long-term functional outcomes. In the collagenase-induced ICH model, misoprostol decreased cellular inflammatory response; attenuated oxidative brain damage and gelatinolytic activity; and decreased high-mobility group box 1 (HMGB1) expression, Src kinase activity, and interleukin-1β expression without affecting cyclooxygenase-2 expression. Furthermore, HMGB1 inhibition with glycyrrhizin decreased Src kinase activity, gelatinolytic activity, neuronal death, and brain lesion volume. Src kinase inhibition with 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) decreased gelatinolytic activity and brain edema and improved neurologic function but did not decrease HMGB1 protein level. These results indicate that misoprostol protects brain against ICH injury through mechanisms that may involve the HMGB1, Src kinase, and matrix metalloproteinase-2/9 pathways.

Topics: Animals; Cerebral Hemorrhage; Disease Models, Animal; Fibroblast Growth Factor 1; Gene Expression; Glycyrrhizic Acid; Inflammation; Interleukin-1beta; Male; Matrix Metalloproteinase 2; Mice, Inbred C57BL; Misoprostol; Neuroprotective Agents; Receptors, Prostaglandin E; src-Family Kinases

Some studies have shown a somatic nociceptive response due to the activation of transient receptor potential A1 channels (TRPA1), which is modulated by the TRPA1 antagonist HC-030031. However, a few studies report the role of TRPA1 in visceral pain. Therefore, we investigated the participation of TRPA1 in visceral nociception and the involvement of nitric oxide, the opioid system and resident cells in the modulation of these channels.. Mice were treated with vehicle or HC-030031 (18.75-300 mg/kg) before ifosfamide (400 mg/kg), 0.75% mustard oil (50 μL/colon), acetic acid 0.6% (10 mL/kg), zymosan (1 mg/cavity) or misoprostol (1 μg/cavity) injection. Visceral nociception was assessed through the electronic von Frey test or the writhing response. Ifosfamide-administered mice were euthanized for bladder analysis. The involvement of nitric oxide and the opioid system were investigated in mice injected with ifosfamide and mustard oil, respectively. The participation of resident peritoneal cells in acetic acid-, zymosan- or misoprostol-induced nociception was also evaluated.. HC-030031 failed to protect animals against ifosfamide-induced bladder injury (p > 0.05). However, a marked antinociceptive effect against ifosfamide, mustard oil, acetic acid, zymosan and misoprostol was observed (p < 0.05). Neither L-arginine (600 mg/kg) nor naloxone (2 mg/kg) could reverse the antinociceptive effect of HC-030031. The reduction of the peritoneal cell population inhibited the acetic acid and zymosan-related writhes without interfering with the misoprostol effect.. Our findings suggest that the blockade of TRPA1 attenuates visceral nociception by a mechanism independent of the modulation of resident cells, nitric oxide and opioid pathways.

Topics: Abdomen; Acetanilides; Animals; Antineoplastic Agents, Alkylating; Cell Count; Colitis; Cystitis; Dinoprostone; Endorphins; Ifosfamide; Inflammation; Male; Mice; Misoprostol; Motor Activity; Mustard Plant; Nitric Oxide; Nociception; Pain; Peritoneal Lavage; Physical Stimulation; Plant Oils; Purines; Transient Receptor Potential Channels; TRPA1 Cation Channel

Among prostaglandins (PGs), PGE2 is abundantly expressed in various malignancies and is probably one of many factors promoting tumor growth by inhibiting tumor immune surveillance. In the current study, we report on a novel mechanism by which PGE2 inhibits in vitro natural killer-dendritic cell (NK-DC) crosstalk and thereby innate and adaptive immune responses via its effect on NK-DC crosstalk. The presence of PGE2 during IFN-γ/membrane fraction of Klebsiella pneumoniae DC maturation inhibits the production of chemokines (CCL5, CCL19, and CXCL10) and cytokines (IL-12 and IL-18), which is cAMP-dependent and imprinted during DC maturation. As a consequence, these DCs fail to attract NK cells and show a decreased capacity to trigger NK cell IFN-γ production, which in turn leads to reduced T-helper 1 polarization. In addition, the presence of PGE2 during DC maturation impairs DC-mediated augmentation of NK-cell cytotoxicity. Opposed to their inhibitory effects on peripheral blood-derived NK cells, PGE2 matured DCs induce IL-22 secretion of inflammation constraining NKp44(+) NK cells present in mucosa-associated lymphoid tissue. The inhibition of NK-DC interaction is a novel regulatory property of PGE2 that is of possible relevance in dampening immune responses in vivo.

Topics: Alprostadil; Bucladesine; Cell Differentiation; Cell Movement; Cells, Cultured; Chemokines; Coculture Techniques; Cytokines; Cytotoxicity, Immunologic; Dendritic Cells; Dinoprostone; Down-Regulation; Gene Expression Regulation; Humans; Immunosuppression Therapy; Inflammation; Interferon-gamma; Killer Cells, Natural; Klebsiella pneumoniae; Misoprostol; Palatine Tonsil; T-Lymphocytes, Helper-Inducer

Pteleopsis suberosa Engl. et Diels (Combretaceae) is a tree distributed in many African countries. The decoction from the stem bark is orally administered for the treatment of gastric ulcers in traditional medicine. Previous pharmacological studies reported the anti-ulcer activity of extracts from P. suberosa stem bark. In the present study, the anti-ulcer and anti-inflammatory effects of the n-butanol fraction (RBuOH) obtained from a methanol extract of P. suberosa bark were investigated on ethanol-induced gastric ulcers in rats and carrageenan-induced paw oedema in mice. Misoprostol (0.50 mg/kg, p.o.) and indomethacin (8.00 mg/kg, p.o.) were used as positive controls for anti-ulcer and anti-inflammatory activities, respectively. Results showed that RBuOH treatment significantly reduced the incidence of gastric lesions (50 mg/kg, P<0.05; 100 and 200 mg/kg, P<0.01) and restored the decreased levels of total sulfhydryl groups (T-SH) and non-protein sulfhydryl groups (NP-SH) (50, 100 mg/kg, P<0.05; 200 mg/kg, P<0.01) in the stomach homogenate. Moreover, RBuOH treatment attenuated MDA levels as index of lipid peroxidation in gastric mucosa. Administration of RBuOH at the same dosage (50, 100 and 200 mg/kg) reduced significantly (P<0.01) carrageenan-induced paw oedema in dose-dependent manner (from 42.81% to 87.81% inhibition, 5h after carrageenan injection). The anti-inflammatory effect of RBuOH at 200 mg/kg was comparable with that of indomethacin. Finally, RBuOH proved to possess elevated free radical scavenger capacity on 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay (IC(50) 23.48 microg/ml) which may contribute to the observed anti-ulcer and anti-inflammatory activities.

Topics: Animals; Anti-Inflammatory Agents; Anti-Ulcer Agents; Antioxidants; Combretaceae; Dose-Response Relationship, Drug; Free Radicals; Indomethacin; Inflammation; Lipid Peroxidation; Male; Mice; Misoprostol; Plant Bark; Plant Extracts; Rats; Rats, Wistar; Stomach Ulcer; Sulfhydryl Compounds

Studies of the molecular and cellular mechanisms of concanavalin A (ConA)-induced liver injury have provided important knowledge on the pathogenesis of many liver diseases involving hepatic inflammation. However, studies identifying hepato-protective factors based on the mechanistic understanding of this model are lacking. Evidence suggests that certain prostaglandin (PG) products of cyclooxygenase (COX)-1 and COX-2 provide important anti-inflammatory and cytoprotective functions in some pathophysiological states. In the present study, we demonstrate a protective role of COX-2 derived PGs in ConA-induced liver injury. COX-2(-/-) mice developed much more severe liver damage upon ConA treatment compared with wild-type and COX-1(-/-) mice. Treatment of COX-2(-/-) mice with misoprostol (a PGE(1/2) analog) or beraprost (a PGI(2) analog) significantly decreased ConA-induced liver injury. Data from both in vivo and in vitro experiments demonstrated that misoprostol and beraprost acted directly on hepatic leukocytes, including natural killer (NK)T and T cells, and down-regulated their production of interferon (IFN)-gamma, which are critical in mediating ConA-induced tissue damage. Collectively, the results provide strong evidence that the protective effects of COX-2 within the liver are mediated through the production of PGE(2) and PGI(2), which exert anti-inflammatory functions. These findings suggest that COX-2-derived PGs may have great therapeutic potentials in treating patients with inflammatory liver diseases.

Topics: Animals; Chemical and Drug Induced Liver Injury; Concanavalin A; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Down-Regulation; Epoprostenol; Gene Expression Regulation; Gene Expression Regulation, Enzymologic; Inflammation; Interferon-gamma; Liver Diseases; Male; Mice; Mice, Knockout; Misoprostol; Mitogens

Interleukin-23, a recently described cytokine produced by activated antigen-presenting cells, including dendritic cells, is a p19/p40 heterodimer. The p40 subunit is shared with IL-12, the major Th1-driving cytokine, while p19 is distantly related to IL-12 p35. IL-23 has pro-inflammatory actions, inducing IL-17 secretion from activated CD4+ T cells, and stimulating the proliferation of memory CD4+ T cells. Here, we examined the effects of PGE2, a well-known immunomodulator, on the production of IL-23 by bone marrow- derived dendritic cells (BM-DCs). Our results indicate that PGE2 increases the production of functional IL-23 from immature BM-DCs in a time- and dose-dependent manner. PGE2 induces both the expression of p19 and p40, without affecting p35 expression. The effect of PGE2 is mediated through the specific receptors EP2/4 and is mimicked by cAMP-inducing agents, such as forskolin and dbcAMP. Although PGE2 also induces IL-1beta and IL-6 expression in non-stimulated DCs, the stimulatory effect of PGE2 on IL-23 production is not mediated through IL-1beta or IL-6. GM-CSF, the pro-inflammatory cytokine required for the generation of BM-DCs, amplifies the IL-23 inducing activity of PGE2 in a synergistic manner. Recent studies described both pro- and anti-inflammatory effects of PGE2, and our results suggest an additional mechanism for its pro-inflammatory role, particularly significant for autoimmune diseases, such as rheumatoid arthritis.

Topics: Alprostadil; Animals; Arthritis; Bone Marrow Cells; Bucladesine; CD4-Positive T-Lymphocytes; Cell Line, Tumor; Cells, Cultured; Colforsin; Culture Media, Conditioned; Cyclic AMP; Dendritic Cells; Dinoprostone; Gene Expression Regulation; Inflammation; Interleukin-12; Interleukin-12 Subunit p35; Interleukin-12 Subunit p40; Interleukin-17; Interleukin-23; Interleukin-23 Subunit p19; Interleukins; Lipopolysaccharides; Male; Mice; Misoprostol; Plasmacytoma; Prostaglandin Antagonists; Protein Subunits; Receptors, Cell Surface; Second Messenger Systems; Specific Pathogen-Free Organisms; Toll-Like Receptor 2; Toll-Like Receptor 4

Effects of misoprostol, a synthetic prostaglandin E1 (PGE1) analogue, on cyclooxygenase-2 (COX-2) protein level and exudate prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) level were investigated in acute carrageenan-induced air pouch inflammation in rats. Treatment with misoprostol (12.5, 25, and 50 microg/kg) has been started in separated groups, 30 min and 2 days before carrageenan injection and it was given twice a day (total of five doses) by orogastric route. Indomethacin, in doses of 0.5 and 5 mg/kg, and specific COX-2 inhibitor SC-58236, in doses of 5, 10, and 20 mg/kg were given 1 h before carrageenan injection by the orogastric route. Misoprostol increased the levels of PGE2 and COX-2 protein at all doses applied. Despite indomethacin and SC-58236 increased the level of COX-2 protein when they used alone, these drugs partially inhibited misoprostol-induced increase in the level of COX-2 protein. Partial inhibition of misoprostol-induced increase in the level of COX-2 protein by indomethacin or SC-58236 may indicate the modulatory roles of endogenous prostaglandins (PGs, especially, PGE2) on the COX-2 expression.

Topics: Animals; Carrageenan; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Drug Combinations; Enzyme Induction; Exudates and Transudates; Female; Indomethacin; Inflammation; Isoenzymes; Leukocyte Count; Leukocytes; Misoprostol; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Rats; Rats, Wistar; Sulfonamides; Thromboxane B2

The effect of single or combined administration of indomethacin and misoprostol on the exudate leukocyte count and thromboxane B2, a stable metabolite of thromboxane A2, and on the leukotriene B4 level, as cyclooxygenase and lipoxygenase metabolites of arachidonic acid, was investigated in acute carrageenan-induced air pouch inflammation in rats. Administration of indomethacin (0.25 to 4 mg/kg) 1 h before carrageenan given by the orogastric route reduced the exudate leukocyte count and thromboxane B2 level whereas it increased the exudate leukotriene B4 level dose dependently. Administration of misoprostol, a synthetic prostaglandin E1 analogue, (12.5 to 100 microg/kg) twice daily for two days before carrageenan given by the orogastric route increased the exudate leukocyte count. Combined misoprostol and indomethacin did not change the effect of indomethacin alone on exudate leukocyte count. Misoprostol, when used alone, decreased exudate thromboxane B2 level significantly. However, misoprostol did not change the exudate leukotriene B4 level, while its combination with indomethacin prevented the indomethacin-induced increase in exudate leukotriene B4 level. In conclusion, although misoprostol can be combined with non-steroidal anti-inflammatory drugs in many chronic inflammatory situations, our results indicate that misoprostol may also be combined with indomethacin in acute inflammation without producing any change on the antiinflammatory efficacy of indomethacin in rats.

Topics: Analysis of Variance; Animals; Anti-Ulcer Agents; Carrageenan; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Excipients; Female; Immunoenzyme Techniques; Indomethacin; Inflammation; Leukocyte Count; Leukotriene B4; Misoprostol; Rats; Rats, Wistar; Thromboxane B2

Prostaglandins appeared protective against acute experimental liver injury of different origin. Misoprostol, stable, orally active, synthetic derivative of PGE1 attenuates several functional alterations in liver mitochondria during ethanol administration. To study its possible hepatoprotective effects on ethanol-induced liver injury in rats we measured: serum activities of alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (GGT) and concentrations of ammonia in blood and liver tissue. Histopathological evaluation of liver slices was also performed. Activities of both enzymes and ammonia values were elevated after intragastric ethanol administration for 60 days. Treatment for 30 days with misoprostol resulted in their decrease. This effect was not observed in the control group. Beneficial results were also obtained in histopathological evaluation of the liver tissue. These results indicate potential therapeutic effects of misoprostol on ethanol-induced liver injury in rats.

Topics: Alanine Transaminase; Ammonia; Animals; Ethanol; gamma-Glutamyltransferase; Inflammation; Liver; Liver Cirrhosis, Experimental; Male; Misoprostol; Rats; Rats, Wistar

The effect of misoprostol (M) on IL-1 beta, TNF-alpha, and lipid mediator release (assessed by RIA) by adherent (assessed by electron microscopy) human monocytes were studied in vitro. Human monocytes stimulated with E. Coli-derived lipopolysaccharide showed an increase in both IL-1 beta and TNF-alpha release. Incubation of the monocytes with LPS and M (18 hrs.), resulted in a reduction of both IL-1 beta and TNF-alpha levels. Leukotriene B4 levels did not increase in response to LPS or M. LPS also caused an increase in thromboxane (TXB2). M decreased TXB2 levels. 6-keto PGF1 alpha (6KP). Incubation with LPS and M stimulated release. LPS caused an increase in PGE2 levels. M (100 microM) caused an increase in PGE2 levels, M (1 microM) had no effect on PGE2. These data suggest a possible immunomodulatory role for misoprostol in inflammatory diseases.

Topics: Escherichia coli; Humans; In Vitro Techniques; Inflammation; Lipopolysaccharides; Misoprostol; Monocytes; Stimulation, Chemical