Effects of several anti-inflammatory drugs on the various parameters involved in the inflammatory response in rat carrageenin-induced pleurisy (original) (raw)
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Life Sciences, 1999
The aim of the present study was to investigate the effect of two inhibitors (3-aminobenzamide and nicotinamide) of poly (ADP-ribose) synthetase on the production of the inflammatory mediator prostaglandins in a model of acute inthunmation, carrageenan-induced pleurisy, where prostaglandms are known to play a crucial role. The results show that the poly (ADP-ribose) synthetase inhibitors, 3-aminob enzamide (2.5, 5 and 10 mg/kg) and nicotinamide (12.5, 25 and 50 mgikg), inhibit the intlammatory response (pleural exudate formation, polymorphonuclear cell intiltration and prostaglandin production). The present results demonstrate that inhibition of poly (ADP-ribose) synthetase exerts potent anti-intlammatory effects. Part of these anti-inflammatory effects may be related to a reduction of prostaglandin production during the inflammatory process.
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.
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
Role of cyclopentenone prostaglandins in rat carrageenin pleurisy
FEBS Letters, 2001
In this study, using rat carrageenin-induced pleurisy, we found that treatment of rats with either indomethacin or NS-398 suppressed the pleurisy at 2 h but significantly exacerbated this reaction at 48 h. Exacerbated inflammation was associated with reduced prostaglandin D(2) levels, decreased heat shock factor 1 (HSF1) activation, reduced hsp72 expression and increased activation of nuclear factor kappaB (NF-kappaB). Replacement of cyclopentenone prostaglandins by treating rats with either prostaglandin J(2) or prostaglandin D(2) reversed the exacerbating effects of cyclooxygenase inhibitors leading to the resolution of the reaction. In conclusion, we demonstrate that cyclopentenone prostaglandins may act as anti-inflammatory mediators by inducing in inflammatory cells HSF1-dependent hsp72 expression and NF-kappaB inhibition, two crucial events for the remission of inflammation.
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.
The protective role of endogenous glutathione in carrageenan-induced pleurisy in the rat
European Journal of Pharmacology, 1999
Peroxynitrite, a potent cytotoxic oxidant formed by the reaction of nitric oxide (NO) with the superoxide anion, was recently proposed to play a major pathogenic role in the inflammatory process. Here we have investigated the effects of endogenous melatonin, a known scavenger of peroxynitrite, in rats subjected to carrageenan-induced pleurisy. Endogenous melatonin was depleted in rats maintained on 24 h light cycle for 1 wk. In vivo depletion of endogenous melatonin enhanced the carrageenan-induced degree of pleural exudation and polymorphonuclear leukocyte migration in rats subjected to carrageenan-induced pleurisy. Lung myeloperoxidase activity and lipid peroxidation were significantly increased in melatonin-deprived rats. However, the inducible NO synthase in lung samples was unaffected by melatonin depletion. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in lungs from carrageenan-treated rats that was markedly enhanced in melatonin-deprived rats. Furthermore, melatonin depletion significantly increased peroxynitrite formation as measured by the oxidation of the fluorescent dye dihydrorhodamine 123, enhanced DNA damage and the decrease in mitochondrial respiration and reduced the cellular levels of NAD؉ in macrophages harvested from the pleural cavity of rats subjected to carrageenaninduced pleurisy. In vivo treatment with exogenous melatonin (15 mg/kg intraperitoneal) significantly reversed the effects of melatonin depletion. Thus, endogenous melatonin plays an important protective role against carrageenan-induced local inflammation.-Cuzzocrea, S., Tan, D.-X., Costantino, G., Mazzon, E., Caputi, A. P., Reiter, R. J. The protective role of endogenous melatonin in carrageenan-induced pleurisy in the rat. FASEB J. 13, 1930 -1938 (1999) 1930 0892-6638/99/0013-1930/$02.25 © FASEB * P Ͻ 0.01 vs. MEL ϩ/ϩ.
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.
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.
Mediators of Inflammation, 2002
BACKGROUND: The model of pleurisy induced by carrageenan exhibits a biphasic response (4 and 48 h) and permits the quantification of exudate, cell migration and certain enzymes such as myeloperoxidase (MPO) and adenosine-deaminase (ADA) that are markers of activated leukocytes. Aims: The present study evaluates whether there exists, in the pleurisy model, a significant inhibition of ADA and MPO enzymes, leukocyte kinetics and other markers of inflammation [nitric oxide (NO) levels, exudation] caused by methotrexate treatment by the intraperitoneal (i.p.) route. Methods: The pleurisy was induced by carrageenan (1%) in mice, and the parameters were analyzed 4 and 48 h after. Results: After the induction of inflammation (4 h), methotrexate (20 mg/kg, i.p., 24 h before pleurisy induction) inhibited the leukocyte infiltration (p < 0.05), NO levels and MPO activity (p < 0.01), but not ADA activity and fluid leakage (p > 0.05). Regarding the second phase of pleurisy (48 h), methotrexate (40 mg/kg, i.p., 0.5 h before pleurisy induction) inhibited the leukocyte infiltration (p < 0.05), fluid leakage, NO levels (p < 0.01), and ADA and MPO activity (p < 0.05). Conclusions: These findings support the evidence that the acute administration of methotrexate has an important systemic anti-inflammatory activity in the studied inflammatory model. This effect was due to a significant inhibition on both neutrophil and mononuclear cells, being less marked in relation to exudation 48 h after. In relation to the enzymes studied and to NO levels, the findings support the evidence that methotrexate inhibits both enzymes (MPO and ADA) from leukocytes at the site of injury, thus reflecting the activation of both neutrophils and lymphocytes, respectively. Furthermore, the inhibiting effect on NO in both phases of pleurisy induced by carrageenan (4 and 48 h) indicates that methotrexate acts on constitutive and/or inducible NO synthases by means of different cells of the pleural cavity.