Pharmacological modulation of Paf-induced rat pleurisy and its role in inflammation by zymosan (original) (raw)
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European Journal of Pharmacology, 1983
Effects of several anti-inflammatory drugs on the various parameters involved in the inflammatory response in rat carrageenin-inducedpleurisy, European J. Pharmacol. 95 (1983) 1-12. In rat carrageenin pleurisy, both steroidal and non-steroidal anti-inflammatory drugs (SAID and NSAID respectively) produced a dose-related reduction of exudate volume and of prostaglandin (PG)E 2 contents in the exudate at 3 h after carrageenin. However, with the exception of ketoprofen, administration of all the NSAID in low doses resulted in a significant reduction of PGE 2 contents with no significant reduction in exudate volume. NSAID reduced leucocyte number and total activities of lysosomal enzymes in the exudate at 3 h after carrageenin only at the higher doses, while SAID did so in a dose-related manner. Both SAID and NSAID reduced the arylsulfatase activity released into the exudate (free activity) dose-relatedly but not the free activity of /3-glucuronidase at 3 h after carrageenin. However, some drug treatments resulted in a lower reduction in free arylsulfatase activity than in exudate volume. These results suggest that the reduction of PGE 2 contents may be the main contribution to the anti-exudative activities of anti-inflammatory drugs in rat carrageenin pleurisy and that this effect may be complemented by the reduction of free activity of lysosomal enzymes such as arylsulfatase.
International Immunopharmacology, 2009
Several studies have shown that the anti-inflammatory effect of Pioglitazone extends beyond the cardiovascular system. This study examines the anti-inflammatory effect of Pioglitazone in comparison to reference drugs (Dexamethasone and Indomethacin) in the mouse model of pleurisy induced by carrageenan which is characterized by two distinct phases (4 and 48 h) of inflammation. Pioglitazone (20 and 50 mg/kg, i.p., 0.5 h before pleurisy) inhibited both neutrophil (4 h) and mononuclears (48 h) influxes (P < 0.01), but not exudation (P > 0.05). While one dose of Pioglitazone was effective in inhibiting inflammation at 4 h, additional doses (10 or 20 mg/kg, i.p., 0.5 h before pleurisy induction followed by either a second dose at 24 h after the first one or two further doses at 12 h of time interval after the first one) were necessary to elicit inhibition of the second (48 h) inflammation phase. These effects were associated with a marked decrease in adenosine-deaminase (ADA) activity, tumor necrosis factor-alpha (TNF-α) and interleukin 1-beta (IL-1β) levels (P < 0.01). Myeloperoxidade (MPO) activity was inhibited only at 4 h (P < 0.05). By contrast, reference drugs were able to inhibit all the studied inflammatory parameters (P < 0.05). These results demonstrated an interesting anti-inflammatory property of this thiazolidinedione class and strengthen prior evidence that PPAR pathways constitute another important route of inflammatory process inhibition of this pleurisy model.
Life Sciences, 2006
Mouse pleurisy induced by carrageenan is used to determine the mechanism of anti-inflammatory action of 7-chloro-5-(4-chlorophenyl)-1,3dihydro-1-methyl-2-H-1,4-benzodiazepin-2 (Ro5-4864). Pre-treatment with Ro5-4864 inhibits different inflammatory parameters, such as neutrophil influx, MPO activity and NO levels in the early phase (4 h), as well as mononuclear cells and ADA activity in the late phase (48 h) of pleurisy. dl-Aminoglutethimide, inhibitor of steroidal synthesis, reverted the effect of Ro5-4864 on these different inflammatory parameters. Our results suggest that anti-inflammatory action of Ro5-4864 may be partly due to its capacity to inhibit leukocyte migration, as well as leukocyte activation and formation of NO by a mechanism dependent on glucocorticoids.
European journal of …, 2000
Carrageenan causes enhanced formation of reactive oxygen species, which contribute to the pathophysiology of inflammation. We have investigated the effects of tempol, a membrane-permeable radical scavenger, in rats subjected to carrageenan-induced pleurisy. Ž. Treatment of rats with tempol 10, 30, or 100 mgrkg 15 min prior to carrageenan attenuated the pleural exudation and the migration of Ž. polymorphonuclear cells caused by carrageenan dose dependently. Tempol also attenuated the lung injury histology as well as the increase in the tissue levels of myeloperoxidase and malondialdehyde caused by carrageenan in the lung. However, tempol did not inhibit the activity of inducible nitric oxide synthase in the lungs. Immunohistochemical analysis for nitrotyrosine revealed positive staining in Ž. lungs from carrageenan-treated rats. Lung tissue sections from carrageenan-treated rats also showed positive staining for poly-ADP-ribose Ž. synthetase PARS. The degree of staining for nitrotyrosine and PARS was markedly reduced in tissue sections obtained from Ž. Ž. carrageenan-treated rats, which had received tempol 100 mgrkg. Furthermore, treatment of rats with tempol significantly reduced i the Ž. Ž. Ž. formation of peroxynitrite, ii the DNA damage, iii the impairment in mitochondrial respiration, and iv the fall in the cellular level of NAD q observed in macrophages harvested from the pleural cavity of rats treated with carrageenan. Tempol also attenuated the cell injury Ž. caused by hydrogen peroxide 1 mM in cultured human endothelial cells. This study provides the first evidence that tempol, a small molecule which permeates biological membranes and scavenges ROS, attenuates the degree of inflammation and tissue damage associated with carageenan-induced pleurisy in the rat. The mechanisms of the anti-inflammatory effect of tempol are discussed.
Analysis of the inflammatory response induced by substance P in the mouse pleural cavity
Peptides, 1999
This study analyzes both cell migration and exudation responses elicited by substance P (SP) in the mouse pleural cavity. SP caused, 4 h after its administration into the mouse pleural cavity, a dose-related recruitment of leukocytes (ED 50 ϭ 14.2 nmol), mainly due to mononuclears. Leukocytes peaked between 2 and 4 h, being followed by a slight decay that remained elevated for up to 24 h. Exudation, although small, was significantly elevated from 2 to 96 h after. NK 1 (FK 888) or NK 3 (SR 142801), but not NK 2 (SR 48968) tachykinin receptor antagonists, significantly inhibited cell migration. HOE 140 and NPC 17731, bradykinin B 2 receptor antagonists, caused graded inhibition of cell influx (ID 50 s of 0.03 and 0.04 pmol), but des-Arg 9-Leu 8-BK, B 1 receptor antagonist, had no effect. The nitric oxide inhibitors L-NOARG and L-NAME, but not D-NAME, significantly inhibited SP-induced pleurisy. Pretreatment of the animals with indomethacin, dexamethasone, terfenadine, theophylline or salbutamol produced significant inhibition of the inflammatory parameters, whereas cromolyn only inhibited exudation. These results indicate that intrapleural injection of SP in mice elicit a long-lasting inflammatory reaction that is characterized by the participation of nitric oxide, kinins, cyclooxygenase metabolites and histamine. Antiasthmatic drugs such as theophylline, salbutamol, dexamethasone, and, to a lesser extent cromolyn, also markedly inhibit this inflammatory reaction. These results provide clear evidence supporting the role played by SP in neurogenic inflammation.
Life Sciences, 2003
In the present study, by comparing the responses in wild-type mice (iNOSWT) and mice lacking (iNOSKO) the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the correlation between endogenous nitric oxide (NO) and prostaglandin (PG) generation in carrageenan-induced pleurisy. The inflammatory response in iNOSKO mice was significantly reduced in respect to iNOSWT animals, as demonstrated by the exudate volume ( À 63%) and numbers of infiltrating cells ( À 62%). The levels of NOx in the pleural exudate from carrageenan-treated mice were significantly (p < 0.01) decreased in iNOSKO mice (16 F 7.6 nmoles/mice) compared to iNOSWT animals (133 F 9 nmoles/mice). Similarly, the amounts of PGE 2 in the pleural exudates of carrageenan-treated animals were significantly (p < 0.01) lower in iNOSKO compared to iNOSWT mice (120 F 20 pg/mice vs. 308 F 51 pg/mice). Also the amounts of 6-keto-PGF 1a produced by lungs from carrageenan-treated iNOSKO mice (1.01 F 0.10 ng/tissue mg) were significantly (p < 0.01) reduced compared to iNOSWT carrageenan-treated mice (2.1 F 0.09 ng/tissue mg). In conclusion our results confirm, by the use of iNOSKO mice that in carrageenan-induced pleurisy NO positively modulates PG biosynthesis. D
Frontiers in Pharmacology
The ecto-5'-nucleotidase (ecto-5'NT/CD73) represents a crucial enzyme for endogenous adenosine generation. Several findings have shown that CD73 plays an important role in regulating vascular permeability and immune cell function. Adenosine 5'-(α,βmethylene)diphosphate (APCP) is a CD73 inhibitor, widely used as pharmacological tool to investigate the role of CD73/adenosine pathway in several in vitro and in vivo models, although it has been also shown to inhibit other ectoenzymes involved in adenosinergic pathway. Here, we evaluated the effect of APCP in the development of inflammation in carrageenan-induced pleurisy model. We found that treatment with APCP (400 μg/ rat) significantly increased cell accumulation, exudate formation, and pro-inflammatory cytokine content into the pleural cavity in the acute phase (4 h) of inflammation, with no differences in the sub-acute phase (72 h) except for the regulation of monocyte chemotactic protein-1 levels. In addition, cells collected by pleural lavage fluids of APCPtreated rats, 4 h following carrageenan injection, showed increased ability to migrate in vitro, both in presence and in absence of N-formyl-L-methionyl-L-leucyl-L-phenylalanine as chemotactic stimulus, compared to cells obtained by control rats. Our results demonstrate that APCP exacerbates the early phase of carrageenan-induced pleurisy by controlling pleural effusion and polymorphonuclear migration in vivo and ex vivo. This effect is likely dependent upon CD73 inhibition, although an inhibitory effect of other ectoenzymes cannot be ruled out.
Inflammation, 2011
The aim of this study was to investigate the anti-inflammatory efficacy of rosiglitazone (ROSI) in a pleurisy model of carrageenan-induced inflammation. Efficacy was monitored in the mouse pleural cavity by evaluating leukocyte migration, exudate concentration, and myeloperoxidase (MPO) and adenosine deaminase (ADA) activities concomitantly with nitrate/nitrite (NOx), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-17A (IL-17A), and vascular endothelial growth factor-alpha (VEGF-α) levels 4 and 48 h after pleurisy induction. In both phases (4 and 48 h) of pleurisy, ROSI inhibited all the inflammation parameters that were tested (p<0.05). These results provide evidence that ROSI was efficacious in inhibiting pro-inflammatory mediators. These anti-inflammatory effects are assumed to mainly result from the inhibition of products released from activated leukocytes, such as MPO, ADA, NOx, TNF-α, IL-1β, IL-17A, and VEGF-α.
Effect of azelastine on platelet-activating factor and antigen-induced pleurisy in rats
European Journal of Pharmacology, 1991
The interference of azelastine with pleurisy induced by antigen was investigated in actively sensitized rats. The antigenic challenge (ovalbumin, 12 irg,Icavity) caused early plasma leakage, which peaked within 4 h. accompanied by intense neutrophil infiltration. Pleural exudate decayed 24 h after antigen prov~ation, when a Iong-Iasting increase in the number of resident eosinophiis was observed. Oral pretreatment with azelastine (l-10 mg/kg) dose dependently inhibited the vasopermeation (ED,, = 4.2 mg/kg) and reduced the pleural exudate (ED5, = 5.8 mg/kg) induced by the antigen. In contrast, azelastine (10 mg/kg) failed to modify the neutrophil influx observed at 4 h and the eosinophil accumulation detected at 24 h. Azelastine was aiso effective against rat pleurisy induced by either platelet-activating factor (PAF-acether& histamine or serotonin. It reduced exudation and the increase in the number of mononuclear cells, neutrophils and eosinophils observed 6 h after PAF-acether. Nevertheless, antagonism of PAF-acether may not be relevant to the inhibition observed in the present model of allsrgic pleurisy, as the inhibition was refractory to three distinct PAF-acether receptor antagonists. In contrast. like azelastine. the histamine ii, receptor antagonist meclizine and the dual histamine and serotonin receptor antagonist cyproheptadine blocked antigen-induced exudation and failed to interfere rt'ith cell influx. We conclude that the anti-exudatory activity of oral azelastine on antigen-induced pleurisy is consistent with it exerting direct effects against vasoactive amines, but is not related to an effect against leucocyte infiltration nor to its ability to inhibit PAF-acether.