Mouse Model Of Carrageenan-induced Pleurisy Research Articles

Bee venom stimulation of a lung meridian acupoint reduces inflammation in a mouse model of carrageenan-induced pleurisy

Bee venom stimulation of a lung meridian acupoint reduces inflammation in a mouse model of carrageenan-induced pleurisy

7-prenyloxi-6-methoxycoumarin from Polygala sabulosa A.W. Bennett Regulates p38 MAPK and NF-kB Pathways Inhibiting the Inflammation Induced by Carrageenan in the Mouse Model of Pleurisy.

Polygala sabulosa, popularly known as "timutu-pinheirinho," has been used in Brazilian folk medicine for the treatment of bowel and kidney disorders and as an expectorant. Evaluate the anti-inflammatory effects of the crude extract (CE), acetonic fraction (Ac), and the main compound, 7-prenyloxi-6-methoxycoumarin (PC) on a mouse model of carrageenan-induced pleurisy. A mouse model of carrageenan-induced pleurisy was used to investigate the effects of P. sabulosa CE, Ac and PC on leukocyte migration, exudate formation, activities of myeloperoxidase (MPO), and adenosine-deaminase (ADA), levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and nitric oxide (NO). In addition, the effect of the plant material on lung histology was also evaluated. The effects of PC on the TNF-α, IL-1β and NO synthase 2 (NOS2) mRNA expression, were also investigated. Finally, the effect of PC on the nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (p38 MAPK) was also evaluated. CE, Ac and PC reduced inflammation in the pleural cavity and lungs. This effect was evidenced by reduction on all inflammatory parameters evaluated; the exception being the inability of the CE to inhibit exudate formation. In isolation, PC showed reduction on mRNA levels of TNF-α, IL-1β and NOS2, and on activation of the NF-κB and p38 MAPK pathways. The presented results show that P. sabulosa has significant anti-inflammatory activity, as does its main compound, PC. Moreover, the results suggest that PC exerts its effects mainly by inhibited the NF-κB and p38 MAPK pathways.

Naringin attenuates the development of carrageenan-induced acute lung inflammation through inhibition of NF-κb, STAT3 and pro-inflammatory mediators and enhancement of IκBα and anti-inflammatory cytokines.

Naringin has been reported to possess diverse pharmacological properties, including anti-arthritic and anti-inflammatory activities. The aim of the present study was to determine the potential anti-inflammatory effect of naringin in a mouse model of carrageenan-induced pleurisy. A single dose of naringin (40 and 80 mg/kg) was administered per oral (p.o.) 1 h before carrageenan (Cg) administration. Pro- and anti-inflammatory cytokines were analysed in pleural fluid. We also assessed the effects of naringin on the expression levels of iNOS, inducible cyclooxygenase isoform (COX-2), ICAM-1, MIP-2, PGE2, STAT3, TGF-β1, nuclear factor kappa B (NF-κB) and inhibitor of kappa B (IκBα) in lung tissue. The histological examinations revealed anti-inflammatory effect of naringin while Cg group deteriorated. Naringin downregulated Th1 and upregulated Th2 cytokines. Western blot analyses revealed increased protein expression of NF-κB, STAT3 and COX-2 and decreased IκBα in response to Cg treatment, which were reversed by the treatment with naringin. In the Cg group, mRNA expression levels of pro-inflammatory mediators upregulated and anti-inflammatory mediators downregulated. Naringin reversed these actions.

Evaluation of Cytotoxic and Anti-Inflammatory Activities of Extracts and Lectins from Moringa oleifera Seeds

BackgroundThe extract from Moringa oleifera seeds is used worldwide, especially in rural areas of developing countries, to treat drinking water. M. oleifera seeds contain the lectins cmol and WSMoL, which are carbohydrate-binding proteins that are able to reduce water turbidity because of their coagulant activity. Studies investigating the ability of natural products to damage normal cells are essential for the safe use of these substances. This study evaluated the cytotoxic and anti-inflammatory properties of the aqueous seed extract, the extract used by population to treat water (named diluted seed extract in this work), and the isolated lectins cmol and WSMoL. Methodology/Principal FindingsThe data showed that the aqueous seed extract and cmol were potentially cytotoxic to human peripheral blood mononuclear cells, while WSMoL and diluted seed extract were not cytotoxic. The M. oleifera aqueous seed extract and the lectins cmol and WSMoL were weakly/moderately cytotoxic to the NCI-H292, HT-29 and HEp-2 cancer cell lines and were not hemolytic to murine erythrocytes. Evaluation of acute toxicity in mice revealed that the aqueous seed extract (2.000 mg/kg) did not cause systemic toxicity. The aqueous seed extract, cmol and WSMoL (6.25 µg/mL) and diluted seed extract at 50 µg/mL exhibited anti-inflammatory activity on lipopolyssaccharide-stimulated murine macrophages by regulating the production of nitric oxide, TNF-α and IL-1β. The aqueous seed extract reduced leukocyte migration in a mouse model of carrageenan-induced pleurisy; the myeloperoxidase activity and nitric oxide, TNF-α and IL-1β levels were similarly reduced. Histological analysis of the lungs showed that the extract reduced the number of leukocytes. Conclusion/SignificanceThis study shows that the extract prepared according to folk use and WSMoL may be non-toxic to mammalian cells; however, the aqueous seed extract and cmol may be cytotoxic to immune cells which may explain the immunosuppressive potential of the extract.

Grape Seed Proanthocyanidin Extract Protects Against Carrageenan-Induced Lung Inflammation in Mice Through Reduction of Pro-inflammatory Markers and Chemokine Expressions

Proanthocyanidins are the most abundant phenolic compounds and have been reported to exert anti-inflammatory actions. The aim of this study was to investigate the effects of grape seed proanthocyanidin extract (GSPE) in a mouse model of carrageenan-induced pleurisy. Following the induction of pleurisy using λ-carrageenan (Cg, 1 %), GSPE (25, 50 and 100 mg/kg) was administered per-oral (p.o.), and the glucocorticoid-induced tumour necrosis factor receptor (GITR), IL-17A expressing cells and other markers, such as cytokines (Th1/Th2 and Th17), were studied. We evaluate the effects of GSPE on the mRNA expression of pro-inflammatory and anti-inflammatory mediators. The results illustrated that the cell numbers of IL-17A and GITR expressing cells and the cytokine levels in Th1/Th17 cells were markedly increased in the Cg-group, whereas the cytokines produced by Th2 cells were significantly decreased in the same group. Treatment with GSPE reversed these effects. Histological examinations revealed anti-inflammatory effects of GSPE.

Anti-inflammatory effects of purine nucleosides, adenosine and inosine, in a mouse model of pleurisy: evidence for the role of adenosine A2 receptors

Adenosine and its metabolite, inosine, have been described as molecules that participate in regulation of inflammatory response. The aim of this study was to investigate the effect of adenosine and inosine in a mouse model of carrageenan-induced pleurisy as well as the participation of adenosine receptors in this response. Injection of carrageenan into the pleural cavity induced an acute inflammatory response characterized by leukocyte migration, pleural exudation, and increased release of interleukin-1β and tumor necrosis factor-α in pleural exudates. The treatment with adenosine (0.3-100 mg/kg, i.p.) and inosine (0.1-300 mg/kg, i.p.) 30 min before carrageenan injection reduced significantly all these parameters analyzed. Our results also demonstrated that A(2A) and A(2B) receptors seem to mediate the adenosine and inosine effects observed, since pretreatment with selective antagonists of adenosine A(2A) (ZM241385) and A(2B) (alloxazine) receptors, reverted the inhibitory effects of adenosine and inosine in pleural inflammation. The involvement of A(2) receptors was reinforced with adenosine receptor agonist CGS21680 treatment, since its anti-inflammatory effects were reversed completely and partially with ZM241385 and alloxazine injection, respectively. Moreover, the combined treatment with subeffective dose of adenosine (0.3 mg/kg) and inosine (1.0 mg/kg) induced a synergistic anti-inflammatory effect. Thus, based on these findings, we propose that inosine contributes with adenosine to exert anti-inflammatory effects in pleural inflammation, reinforcing the notion that endogenous nucleosides play an important role in controlling inflammatory diseases. This effect is likely mediated by the activation of adenosine A(2) subtype receptors and inhibition of production or release of pro-inflammatory cytokines.

CGS 21680, an agonist of the adenosine (A2A) receptor, decreases acute lung inflammation

Adenosine A2A receptor agonists may be important regulators of inflammation. The aim of this study was to investigate the effects of CGS 21680 (0.1mg/kgi.p.), an agonist of the adenosine (A2A) receptor, in a mouse model of carrageenan-induced pleurisy. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterised by: infiltration of neutrophils in lung tissues and subsequent lipid peroxidation, increased production of nitric oxide (NO), cytokines such as tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and increased expression of intercellular adhesion molecule (ICAM-1) and platelet-adhesion molecule (P-selectin). Furthermore, carrageenan induced the expression of nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS), nitrotyrosine, the activation of poly-ADP-ribosyl polymerase (PARP), as well as induced apoptosis (FAS-ligand expression, Bax and Bcl-2 expression) in the lung tissues. Administration of CGS 21680, 30min prior to challenge with carrageenan, caused a significant reduction of all the parameters of inflammation measured. In addition, to confirm the anti-inflammatory effect of CGS 21680, we have also evaluated the effects of CGS 21680 post-treatment (30min after the challenge with carrageenan) and we have demonstrated that also it caused a reduction of neutrophil infiltration and the degree of lung injury. Thus, based on these findings we propose that adenosine A2A receptor agonists such as CGS 21680 may be useful in the treatment of various inflammatory diseases.

The effects of oleuropein aglycone, an olive oil compound, in a mouse model of carrageenan-induced pleurisy

Several olive oil phenolic compounds, such us oleuropein have attracted considerable attention because of their antioxidant activity, anti-atherosclerotic and anti-inflammatory properties. The aim of this study was to investigate the effects of oleuropein aglycone, a hydrolysis product of oleuropein, in a mouse model of carrageenan-induced pleurisy. Mice were anaesthetized and subjected to a skin incision at the level of the left sixth intercostals space. The underlying muscle was dissected and saline or saline containing 2% λ-carrageenan was injected into the pleural cavity. Injection of carrageenan elicited an acute inflammatory response characterized by: infiltration of neutrophils in lung tissues (P<0.01 versus sham. P<0.01 versus carrageenan) and subsequent lipid peroxidation (P<0.01 versus sham. P<0.01 versus carrageenan), increased production of tumor necrosis factor-α and interleukin-1β (P<0.01 versus sham. P<0.01 versus carrageenan), increased expression of adhesion molecules, increased synthesis of nitric oxide (P<0.01 versus sham. P<0.01 versus carrageenan), nitrotyrosine and poly-ADP-ribose (P<0.01 versus sham. P<0.01 versus carrageenan). Administration of oleuropein aglycone 30min after the challenge with carrageenan, caused a significant reduction of all the parameters of inflammation measured. Thus, we propose that olive oil phenolic constituents may be useful in the treatment of various inflammatory diseases.

Effect of apocynin, a NADPH oxidase inhibitor, on acute lung inflammation

NADPH-oxidase is an enzyme responsible for reactive oxygen species production (ROS) and inhibition of this enzyme represents an attractive therapeutic target for the treatment of many diseases. The aim of this study was to investigate the effects of apocynin, a NADPH-oxidase inhibitor, in a mouse model of carrageenan-induced pleurisy. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: infiltration of neutrophils in lung tissues and subsequent lipid peroxidation, increased production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and increased expression of intercellular adhesion molecule (ICAM-1) and platelet-adhesion molecule (P-selectin). Furthermore, carrageenan induced the expression of nuclear factor-κB (NF-κB) inducible nitric oxide synthase (iNOS), nitrotyrosine, poly-ADP-ribosyl polymerase (PARP) as well as induced apoptosis (TUNEL staining, FAS-ligand expression, Bax and Bcl-2 expression) and mitogen-activated protein kinase (MAPK) activation in the lung tissues. Administration of apocynin, 30 min after the challenge with carrageenan, caused a significant reduction of all the parameters of inflammation measured. Thus, based on these findings we propose that NADPH oxidase inhibitor such as apocynin may be useful in the treatment of various inflammatory diseases.

Inhibition of glycogen synthase kinase‐3β attenuates the development of carrageenan‐induced lung injury in mice

Glycogen synthase kinase-3 (GSK-3) is a ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and has recently been implicated in the pathophysiology of a number of diseases. The aim of this study was to investigate the effects of GSK-3beta inhibition in a model of acute inflammation. Here, we have investigated the effects of TDZD-8, a potent and selective GSK-3beta inhibitor, in a mouse model of carrageenan-induced pleurisy. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by: accumulation of fluid containing a large number of neutrophils (PMNs) in the pleural cavity, infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx), prostaglandin E2 (PGE2), tumour necrosis factor-alpha, (TNF-alpha) and interleukin-1beta (IL-1beta). Furthermore, carrageenan induced an upregulation of the adhesion molecules ICAM-1 and P-selectin, iNOS, COX-2 as well as nitrotyrosine as determined by immunohistochemical analysis of lung tissues. Administration of TDZD-8 (1, 3 or 10 mg kg(-1), i.p.), 30 min prior to injection of carrageenan, caused a dose-dependent reduction in all the parameters of inflammation measured. Thus, based on these findings we propose that inhibitors of the activity of GSK-3beta, such as TDZD-8, may be useful in the treatment of various inflammatory diseases.