thromboxane-b2 and Pleurisy

This study evaluates the action of celecoxib and rofecoxib, two selective cyclooxygenase-2 (COX-2) inhibitors in two acute models of inflammation, carrageenan (Cg)-induced rat pleurisy, and paw oedema formation.. Male Wistar rats (N = 4-10 per group) were used. A fixed volume of PBS or carrageenan was injected into the pleural cavity or into the paw. Furthermore, the myeloperoxidase (MPO) activity and the levels of nitrite/nitrate (NOx), interleukin-1beta (IL-1beta), tumor necrosis factor-a (TNF-a) and PGE2 were also assessed in the paw tissue or in pleural exudate.. Dexamethasone (DEX, 0.5 mg kg(-1), s.c., -4 h) and indomethacin (INDO, 3 mg kg(-1), p.o., -1 h) suppressed Cg-induced pleural exudate accumulation by 84 and 77% and inflammatory cell influx by 66 and 47%, respectively. In contrast, celecoxib (CLX, 10 mg kg(-1), p.o., -1 h) or rofecoxib (RFX, 10 mg kg(-1) , p.o., -1 h) only reduced the Cg-induced pleural exudate volume by 44 and 40%, respectively, but had no significant effect over inflammatory cell influx. At the same doses used for pleurisy, DEX, INDO, CLX, RFX and SC-560 (a selective COX-1 inhibitor, 40 mg kg(-1), p.o., -1 h), inhibited the Cg-induced paw oedema by 49, 31, 21, 21 and 17%. DEX, INDO or SC-560 reduced the level of MPO by 71, 78 and 59%, while CLX or RFX produced a small, but significant increase (28 or 16%) in MPO activity. In the rat model of pleurisy, PGE2 levels in cell-free exudates were significantly attenuated by 91, 89, 57 and 65% in animals treated with DEX, INDO, CLX or RFX. In contrast, INDO reduced significantly the whole bloodTXB, synthesis (59%) while DEX and INDO reduced the pleural content of NOx significantly. Treatment of animals with CLX or RFX did not alter the content of pro-inflammatory cytokines IL-1beta or TNF-alpha in the pleural exudate, but CLX reduced IL-1beta levels in the rat paw tissue and RFX increased TNF-alpha in this tissue.. Together these results provide consistent evidence indicating that the selective COX-2 inhibitors CLX and RFX, in contrast to DEX, INDO or SC-560, despite reducing greatly the Cg-induced pleural exudation, PGE2 content and paw oedema have only partial acute anti-inflammatory properties in two different rat acute models of inflammation.

Topics: Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Celecoxib; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dexamethasone; Dinoprostone; Edema; Indomethacin; Inflammation; Interleukin-1; Isoenzymes; Lactones; Male; Nitric Oxide; Peroxidase; Pleurisy; Prostaglandin-Endoperoxide Synthases; Pyrazoles; Rats; Rats, Wistar; Sulfonamides; Sulfones; Thromboxane B2; Tumor Necrosis Factor-alpha

Amtolmetin guacyl (CAS 873344-06-7, MED 15) is a non-steroidal anti-inflammatory drug (NSAID) which has shown gastroprotective effects attributable to capsaicin receptor stimulation through the presence of a vanillic moiety in its molecular structure. The present paper further defines the anti-inflammatory activity of the product in an exudative rat model and in an arthritic rat model. The results obtained from both studies demonstrate anti-inflammatory effects comparable to those of the traditional NSAIDs in use. This study also demonstrated that amtolmetin guacyl possesses high antiaggregatory activity comparable to acetylsalicylic acid (CAS 50-78-2), when expressed as inhibition of blood thromboxane synthesis; the in vitro antiaggregatory activity was decidedly superior to that expressed by either acetylsalicylic acid or tolmetin (CAS 26171-23-3) (a traditional NSAID and metabolite of amtolmetin guacyl). The characteristics of gastroprotection along with control of inflammation and platelet aggregation render amtolmetin guacyl recommendable in the treatment of inflammatory and thromboembolic conditions where long-term therapy is required.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Arthritis; Body Weight; Bone Density; Carrageenan; Dose-Response Relationship, Drug; Exudates and Transudates; Glycine; In Vitro Techniques; Indomethacin; Male; Piroxicam; Platelet Aggregation; Platelet Aggregation Inhibitors; Pleurisy; Pyrroles; Rats; Thromboxane B2

The present study examined the inhibitory profiles of NS-398 and nimesulide against prostaglandin (PG) formation in inflammatory and non-inflammatory sites, and compared them with those of aspirin and indomethacin. In vitro, indomethacin inhibited PGH synthase (PGHS)-1 and PGHS-2 almost equally, while NS-398 and nimesulide inhibited only PGHS-2. NS-398 (1, 10 mg/kg) and nimesulide (3 mg/kg) slowed the rate of plasma exudation and thus the exudate accumulation in rat carrageenin-induced pleurisy. Aspirin (30, 100 mg/kg) and indomethacin (10 mg/kg) also reduced this rate. NS-398 and nimesulide reduced the PGE2 more potently than TXB2 and 6-keto-PGF1 alpha in the exudate. However, aspirin and indomethacin did not exhibit this selectivity. The levels of PGE2 correlated significantly with the plasma exudation rate. Moreover, nimesulide (3 mg/kg) did not affect PGE2 formation in rat stomachs injected with 1 M NaCl solution, while indomethacin (10 mg/kg) reduced it. Thus, NS-398 and nimesulide exhibit different inhibitory profiles from aspirin and indomethacin against PG formation. These results suggest that PGE2 may be produced by PGHS-2 in the inflammatory site, and may play a more prominent role than PGI2 in plasma exudation.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; Dose-Response Relationship, Drug; Gastric Juice; Indomethacin; Isoenzymes; Male; Membrane Proteins; Nitrobenzenes; Pleurisy; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Rats; Rats, Sprague-Dawley; Sodium Chloride; Sulfonamides; Thromboxane B2

Extra-cellular and cell-associated Ca(2+)-dependent phospholipases A2 and released thromboxane B2 were correlated to exudation and cell migration during rat pleurisy induced by carrageenan or zymosan. Extra-cellular phospholipase A2 was delayed with respect to acute inflammation, while cell-associated phospholipase A2 closely correlated with cell migration and thromboxane B2 levels. This confirms that the subcellular localization of phospholipases A2 is linked to their physiological action and, in particular, suggests that the cell-associated, rather than the extracellular enzyme, accounts for the production of eicosanoids.

Topics: Animals; Biomarkers; Carrageenan; Enzyme Activation; Extracellular Space; Exudates and Transudates; Kinetics; Male; Phospholipases A; Phospholipases A2; Pleurisy; Prostaglandin-Endoperoxide Synthases; Radioimmunoassay; Rats; Rats, Wistar; Thromboxane B2; Zymosan

The anti-inflammatory effects of Ph CL28A, a potentiator of prostacyclin output and inhibitor of leukotriene (LT) synthesis, were assessed in two models of acute inflammation. In paw oedema induced by carrageenan in rats, Ph CL28A (10-100 mg/kg), given i.p. at the same time as the carrageenan, inhibited oedema for up to 4 h. When indomethacin or Ph CL28A was given locally into the paw with carrageenan, indomethacin inhibited oedema formation but Ph CL28A potentiated the oedema for up to 4 h. As Ph CL28A does not inhibit cyclo-oxygenase, its anti-inflammatory effects in this model may reflect its ability to increase prostacyclin output. In pleurisy induced by carrageenan in rats, there were increases in leukocytes, LTB4, thromboxane B2 (TxB2) and 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) in the pleural fluid over 3 h. In this model, Ph CL28A (30 mg/kg) given i.p. decreased leukocyte numbers and LTB4 but did not affect TxB2 or 6-oxo-PGF1 alpha. Indomethacin decreased both prostanoids but did not affect leukocyte accumulation. The beneficial effects of Ph CL28A in two different models of acute inflammation suggests that it may have potential as an anti-inflammatory agent.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Azo Compounds; Blood Pressure; Carrageenan; Edema; Epoprostenol; Hydroxyprostaglandin Dehydrogenases; Indomethacin; Leukotriene B4; Male; Pleurisy; Radioimmunoassay; Rats; Rats, Wistar; Thromboxane B2

A series of pyrazolo[1,5-a]pyrimidin-7-ones (1c-17c) were synthesized to evaluate in vivo and in vitro effects induced by structural modifications at the 2 position of 4,7-dihydro-4-ethyl-2-phenylpyrazolo[1,5-a]pyrimidin-7-one (FPP028). This substance, which has been previously studied, is a weak inhibitor of prostaglandin biosynthesis and a nonacid analgesic and anti-inflammatory agent devoid of ulcerogenic properties. To gain more insight into the mechanism of action of this class of compounds, several in vivo tests were carried out, such as carrageenan-induced rat paw edema and pleurisy. In vitro tests include some studies of leukocyte functions, such as superoxide production and myeloperoxidase release. In vitro effects on arachidonic acid-, adenosine 5'-diphosphate-, and platelet-activating factor-induced platelet aggregation were also studied. Different anti-inflammatory activities were observed, depending on the nature of substituents at the 2 position; these differences are probably linked to the capacity of these compounds to inhibit leukotrienes and/or prostaglandin biosynthesis with different selectivity. 4,7-Dihydro-4-ethyl-2(2-thienyl)pyrazolo[1,5-a]pyrimidin-7-one (7c) proved to be the most interesting compound of the novel synthesized series, showing powerful pharmacological activity in vivo as well as in vitro, together with very weak acute toxicity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Platelets; Chemotaxis, Leukocyte; Edema; Humans; In Vitro Techniques; Leukotriene B4; Neutrophils; Peroxidase; Platelet Aggregation Inhibitors; Pleurisy; Pyrazoles; Pyrimidines; Rats; Rats, Wistar; Superoxides; Thromboxane B2

L-PIA, a standard A1-selective adenosine agonist, was evaluated orally in carrageenan (CRG)- and reverse passive arthus-pleurisy. White blood cell (WBC) and exudate accumulation were assessed four hours after induction of the inflammatory response. L-PIA inhibited WBC accumulation in both models with ID50's of 4.37 and 4.42 mg/kg, respectively. In contrast, exudate was inhibited by L-PIA only in the CRG pleurisy model (ID50 = 1.01 mg/kg). In mechanistic studies, L-PIA reversed the drop in circulating neutrophil count which occurred within 15 minutes after CRG injection, suggesting that L-PIA may inhibit adhesion of the cells to the endothelium. The effects of L-PIA on several parameters of rat neutrophil function were determined. Enzyme release, O2-, TXB2, and LTB4 production were monitored in response to FMLP and opsonized zymosan (SOZ) stimulation. At high concentrations, L-PIA had a mild inhibitory effect on O2- release in response to FMLP and had a moderate effect on arachidonic acid metabolite production in response to both stimuli. The other response were unaffected. These results suggest that L-PIA may prevent diapedisis or neutrophil adhesion to the endothelium, but has a minimal effect on enzyme release, O2-, LTB4 and TXB2 production.

Topics: Adenosine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthus Reaction; Carrageenan; Exudates and Transudates; In Vitro Techniques; Leukocytes; Male; Neutrophils; Oxygen Consumption; Pleurisy; Rats; Rats, Inbred Strains; Receptors, Purinergic; Thromboxane B2

We have compared the early development (0-4h) of two acute non-specific inflammatory reactions induced by the intrapleural injection of isologous serum or a suspension of CaPP crystals. The intensity of the reactions was assessed in terms of the exudate volume, the number and ratio of pleural cells and different cell functions and secretions. The number of exudative cells elicited by isologous serum was higher than with CaPP but the PMN/Monocytes ratio was the same. The amount of protein in the serum-induced exudate was constant from 1 h to 4 h and was similar in the CaPP-induced pleural exudate at the latter time. The amount of complement increased similarly in the two models. The chemotactic potency of the exudates and cell supernatants following incubation showed similar values in the two models. Eicosanoid levels were higher in CaPP--than in isologous serum-induced exudates. Prostacyclin and peptidoleukotrienes were released in specially large amounts at the very outset of the inflammatory reactions.

Topics: Acute Disease; Animals; Calcium Phosphates; Cells, Cultured; Eicosanoids; Epoprostenol; Leukocytes, Mononuclear; Leukotriene B4; Male; N-Formylmethionine Leucyl-Phenylalanine; Pleurisy; Rats; Rats, Inbred Strains; SRS-A; Thromboxane B2

The racemic compound indobufen and its (+)- and (-)-enantiomers have been compared for their effects on blood platelet function and rat carrageenan pleurisy. The antiplatelet properties were studied in-vitro in human platelets by measuring the inhibition of platelet aggregation and generation of serum thromboxane (Tx) B2. In-vivo, the antiplatelet and anti-inflammatory properties were studied in rats by measuring the inhibition of serum TxB2, the amount of 6-keto-PGF1 alpha in pleural exudate and pleural exudate volume. In all tests the (+)-enantiomer was slightly more potent than the racemate, while the (-)-enantiomer was far less potent. In the same rats, treatment with the lowest doses of the compounds giving 90% inhibition of serum thromboxane B2 generation was associated with occasional macroscopic lesions of the gastric mucosa.

Topics: Animals; Gastric Mucosa; Humans; Isoindoles; Phenylbutyrates; Platelet Aggregation; Platelet Aggregation Inhibitors; Pleurisy; Rats; Rats, Inbred Strains; Stereoisomerism; Thromboxane B2

Topics: Animals; Bradykinin; Captopril; Exudates and Transudates; Histamine Release; Indomethacin; Kaolin; Kinins; Male; Pleurisy; Prostaglandins; Radioimmunoassay; Rats; Rats, Inbred Strains; Thromboxane B2

A single injection of a streptococcal preparation, OK-432, with fresh frozen plasma (FFP) (or fresh human serum) into the peritoneal or pleural cavity for the treatment of malignant ascites or pleurisy resulted in a complete reduction of ascitic fluid or pleural effusion in 5 out of 11 patients. FFP was used a further source of complement for the effective accumulation of antitumor polymorphonuclear leukocytes (PMNs) by complement-derived chemotactic factors in the cavity. C5a increased in the fluids 3-9 h after the injection and preceded a massive increase in PMNs. C1 inhibitor (C1INH) and C3b inactivator (C3bINA) decreased in several cases 6 h after the treatment. Chemotactic arachidonic acid metabolites, thromboxane B2(TXB2) as a characteristics of TXA2, and leukotriene B4(LTB4) also increased at the same time even in cases where C5a changed only minimally, and may play a role in accumulating antitumor PMNs in the cavity.

Topics: Adult; Aged; Aged, 80 and over; Ascites; Biological Products; Complement Activation; Complement C5; Complement C5a; Female; Freezing; Humans; Immunization, Passive; Leukotriene B4; Male; Middle Aged; Neoplasms; Neutrophils; Picibanil; Pleurisy; Thromboxane B2

During the development of an acute inflammatory reaction induced in the rat pleural cavity by dextran, calcium pyrophosphate, saline or phosphate buffered saline, macrophages present at a distant site (peritoneal cavity) display an increased capacity to release prostanoids: prostaglandins, prostacyclin and thromboxane. Enhanced levels of 6-keto-PGF1 alpha were observed both in peritoneal lavages (experiments in vivo) and in macrophage supernatants after 24-h culture (experiments in vitro). TXB2 levels were mainly increased in peritoneal lavages and PGE2 in culture supernatants. In vivo, levels of prostanoids in the peritoneal cavity reached a maximum 24 h after the induction of pleurisy whatever the injected substance. In vitro, amounts of arachidonic acid metabolites were highest in supernatants of cultured peritoneal macrophages harvested 72 h after the pleural injection of dextran or CaPP. These results show that the regulation of macrophage functions is closely related to prostanoid production, especially the release of PGE2 and PGI2.

Topics: Animals; Dinoprost; Dinoprostone; Macrophages; Male; Peritoneal Cavity; Pleurisy; Prostaglandins; Prostaglandins F; Rats; Rats, Inbred Strains; Thromboxane B2; Time Factors

Pleurisy was induced in rats by an intrapleural injection of 0.5 ml of 1% kaolin. The exudation of plasma into the pleural cavity showed two peaks at 20 min and 3-5 h after the kaolin injection. The volume of the pleural fluid increased gradually up to 5 h. The effects of treatment with mepyramine, methysergide, captopril, bromelain and indomethacin suggested that the early phase (20 min) of exudation was mediated mainly by kinins, histamine and 5-HT, and that the late phase (3 h) was mediated by prostaglandins (PGs) and possibly kinins. We measured the levels of histamine, kinin and PG in the pleural exudate to verify the involvement of the mediators mentioned above. Intracellular histamine levels decreased markedly and extracellular histamine levels increased significantly 20 min after the induction of kaolin pleurisy. Only threshold levels of kinin were detected after the induction of pleurisy. Captopril treatment, however, increased kinin levels which peaked at 20 min and decreased rapidly thereafter. Levels of 6-keto-PGF1 alpha and thromboxane B2 showed a peak at 20 min, whereas levels of PGE2 increased gradually from 20 min to 5 h. These results indicate that kaolin-induced pleurisy is a kinin-related inflammation and could be used as a model for studying the in vivo interaction of the kallikrein-kinin system and PGs at inflammatory sites.

Topics: Animals; Bromelains; Captopril; Exudates and Transudates; Histamine; Immunoenzyme Techniques; Indomethacin; Kaolin; Kinins; Male; Methysergide; Pleurisy; Pyrilamine; Radioimmunoassay; Rats; Rats, Inbred Strains; Thromboxane B2; Time Factors

Topics: 6-Ketoprostaglandin F1 alpha; Acupuncture Therapy; Animals; Carrageenan; Electric Stimulation; Exudates and Transudates; Female; Pleura; Pleurisy; Rats; Rats, Inbred Strains; Thromboxane B2

Injection of platelet-activating factor (PAF-acether) into the pleural cavity of rats induced the accumulation of a moderately intense exudate within 30 to 60 minutes. By comparison with animals given injections of the vehicle alone, the animals given this mediator had elevated levels of leukotriene C4-immunoreactive material (LTC4 im) in the exudate and decreased quantities of thromboxane B2 (TxB2) and of 6-Keto-F1 alpha-prostaglandin (6-Keto PGF1 alpha). Nifedipine, verapamil, and diltiazem reduced the pleural exudate with no major effect on the mediators. Both salbutamol and theophylline reduced the exudate and the levels of LTC4 im. Acetylsalicylic acid, phenylbutazone and indomethacin significantly inhibited the exudate, greatly lowered the quantities of cyclooxygenase derivatives and tended to increase LTC4 im. Phenidone, which inhibits the cyclooxygenase and lipoxygenase pathways, decreased the exudate and the three mediators. The phospholipase A2 inhibitor, chloroquine, decreased both the amount of exudate and moderately the concentration of LTC4 im. The glucocorticoids studied had no effect on the exudate or on the mediators. These results suggest that the role of the increased LTC4 im in the induction of the pleurisy is not clear.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents, Non-Steroidal; Calcium Channel Blockers; Exudates and Transudates; Glucocorticoids; Male; Platelet Activating Factor; Pleurisy; Rats; Rats, Inbred Strains; SRS-A; Thromboxane B2; Time Factors; Vasodilator Agents

Carrageenin pleurisy was induced in adrenalectomised (ADX) and sham-operated (SHO) rats. The magnitude and duration of inflammation, as estimated by fluid exudation and cell migration, was greatly increased (approximately doubled) in ADX rats compared with that in their SHO controls. The content of eicosanoids (6-keto-prostaglandin F1 alpha (6-keto-PGF 1 alpha), thromboxane B2 (TXB2), and leukotriene B4 (LTB4] in inflammatory exudates from ADX rats was significantly (2-4 fold) greater than that of their SHO controls. Resident macrophages obtained from ADX rats produced more eicosanoids per cell per unit time when stimulated in vitro with zymosan, than did cells from the SHO controls. Administration of glucocorticoids blocked the inflammatory response and reduced the release of eicosanoids both in vitro and in vivo in both groups of rats. These data are consistent with the notion that physiological amounts of glucocorticoids exert a tonic inhibitory action on phospholipase activity in normal animals and that the increased secretion of these hormones during the inflammatory response serves to check and control the development of inflammation.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adrenalectomy; Animals; Annexins; Carrageenan; Glucocorticoids; Glycoproteins; In Vitro Techniques; Inflammation; Leukotriene B4; Phospholipases A; Pleurisy; Rats; Thromboxane B2

Rat pleurisy was induced by intrapleural injection of phorbol myristate acetate (PMA), a known tumor promotor and a component of croton oil. Pleural fluids at 30 min and 1 hr after PMA-injection were collected and arachidonic acid metabolites in the fluids were measured by RIA or bioassay after fractionation through reversed phase HPLC using an ODS column. The major metabolites found in the pleural fluid were 6-keto-PGF1 alpha, TXB2 and PGD2, with a small amount of PGE2. Pretreatment with 10 mg/kg indomethacin suppressed the pleural fluid accumulation and also reduced the amount of the above metabolites to the basal levels. Treatment with OKY-046, a novel thromboxane synthetase inhibitor, reduced the level of TXB2 completely, but had no effect on those of 6-keto-PGF1 alpha and PGD2, and it had no effect on pleural fluid accumulation either. The results may indicate that PGI2 plays a role for the vascular permeability increase in the early phase of pleurisy.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Anti-Inflammatory Agents; Arachidonic Acid; Arachidonic Acids; Chromatography, High Pressure Liquid; Inflammation; Male; Platelet Aggregation; Pleurisy; Prostaglandin D2; Prostaglandins D; Radioimmunoassay; Rats; Rats, Inbred Strains; Tetradecanoylphorbol Acetate; Thromboxane B2

The cellular origin and kinetics of TXB2 and 6-keto PGF1 alpha in carrageenan-induced pleurisy has been studied. Maximum levels of these prostanoids occurred 1 hour after induction of pleurisy. Mononuclear cells initially present in the pleural cavity synthesized TXB2 and 6-keto PGF1 alpha from (14C) arachidonic acid. By contrast, PMN cells harvested 6 hours after the induction of inflammation did not produce 6-keto-PGF1 alpha. Selective inhibition of thromboxane synthetase with drugs in vitro and in vivo increased the formation of 6-keto-PGF1 alpha, the stable breakdown product of PGI2. This metabolic effect was parallel to an increase in the volume of exudate and in PMN migration. These results suggest that TXA2 seems to be implicated not only as a chemotactic agent but also as an antagonist of PGI2 vasodilator effects.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Arachidonic Acids; Carrageenan; Epoprostenol; Exudates and Transudates; Leukocytes; Male; Pleurisy; Rats; Rats, Inbred Strains; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes

Injection of lambda-carrageenin into the pleural cavity of rats caused the accumulation of the pleural exudate. When levels of prostaglandins (PGs) and thromboxane (TX) B2 were quantified by gas chromatography-mass spectrometry as their methyl ester (ME)-dimethylisopropylsilyl (DMiPS) ether or ME-methoxime-DMiPS ether derivatives, 6-keto-PGF1 alpha reached the maximum at 1 hr after carrageenin, then PGE2 and TXB2 showed peaks at 3 hr and waned off before 9 hr. The PGF/ alpha level was kept low, but PGD2, PGE1 and PGF1 alpha were not detected. Aspirin (100 mg/kg, i.p.) significantly decreased the PG and TXB2 levels and suppressed the rate of plasma exudation until 5 hr, but did not at 7 hr, when it was measured by the amount of exuded pontamine sky blue injected intravenously. OKY-025 (300 mg/kg, i.p.), a selective TXA synthetase inhibitor, and tranylcypromine (20 mg/kg, i.p.), a PGI synthetase inhibitor, could not extensively inhibit the accumulation of the exudate. These results suggest that the cyclooxygenase products of arachidonic acid, particularly PGE2, definitely play an important role in the exudation during the first 5 hr.

Topics: Animals; Aspirin; Carrageenan; Gas Chromatography-Mass Spectrometry; Imidazoles; Male; Pleurisy; Prostaglandins; Rats; Rats, Inbred Strains; Thromboxane B2; Thromboxane-A Synthase; Thromboxanes

Topics: Animals; Aspirin; Butylated Hydroxytoluene; Carrageenan; Disease Models, Animal; Imidazoles; Inflammation; Pleural Effusion; Pleurisy; Prostaglandin Endoperoxides; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Thromboxane B2; Thromboxanes