Reduction of carrageenan-induced acute pulmonary inflammation in mice by novel thiazolidinedione derivative LPSF/RA-4

A number of studies have demonstrated the biological activities of peroxisome proliferator-activated receptors. However, few studies have addressed the effects of the agonists of these receptors on lung diseases. The aim of the present study was to evaluate the anti-inflammatory action of a novel sy...

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Published in:	European journal of pharmacology Vol. 718; no. 1-3; pp. 197 - 205
Main Authors:	Barbosa, Karla P.S., Santos, Laise A.M., Ribeiro, Edlene L., Fragoso, Ingrid T., Rocha, Sura W.S., Nunes, Ana K.S., França, Maria E.R., Silva, Bruna S., Silva, Amanda K.S.e., Donato, Mariana A.M., Gomes, Fabiana O.S., Silva, Teresinha G., Pitta, Ivan R., Pitta, Marina R., Lima, Maria C.A., Uchôa, Flávia D.T., Galdino, Suely L., Peixoto, Christina A.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 15-10-2013
Subjects:	Acute Disease Acute lung injury agonists Animals carrageenan Carrageenan - adverse effects edema Gene Expression Regulation, Enzymologic - drug effects histopathology immunohistochemistry Indoles - pharmacology Indoles - therapeutic use indomethacin inducible nitric oxide synthase Inflammation Mediators - metabolism interleukin-1beta Leukocyte Count leukocytes Leukocytes, Mononuclear - cytology Leukocytes, Mononuclear - drug effects Leukocytes, Mononuclear - immunology light microscopy Lung - drug effects Lung - pathology Male Mice nitric oxide Nitric Oxide - metabolism Peroxisome proliferator-activated receptor Pleurisy Pleurisy - chemically induced Pleurisy - drug therapy pneumonia Pneumonia - blood Pneumonia - chemically induced Pneumonia - drug therapy Pneumonia - genetics receptors Thiazolidinedione Thiazolidinediones - pharmacology Thiazolidinediones - therapeutic use transmission electron microscopy tumor necrosis factor-alpha Western blotting Acute lung injury Peroxisome proliferator-activated receptor Thiazolidinedione Pleurisy
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Summary:	A number of studies have demonstrated the biological activities of peroxisome proliferator-activated receptors. However, few studies have addressed the effects of the agonists of these receptors on lung diseases. The aim of the present study was to evaluate the anti-inflammatory action of a novel synthetic thiazolidine derivative (5Z)-3-benzyl-5-(1H-indol-3-ylmethylene)-thiazolidine-2,4-dione (LPSF/RA-4) on acute lung inflammation (pleurisy) induced by carrageenan. Forty mice were randomly allocated to the following groups: (I) saline control group (sham); (II) carrageenan (CAR) group; (III) CAR+LPSF/RA-4 group treated with LPSF/RA-4 (60μmol/kg); and (IV) INDO group treated with indometacin (5mg/kg). Total cell counts and the measure of nitric oxide (NO) were performed in pleural exudates. Lung fragments were processed for light microscopy, transmission electron microscopy, immunohistochemistry and Western blotting. The influx of leucocytes and NO levels were significantly reduced following treatment with LPSF/RA-4 and INDO. Histopathological and ultrastructural analyses of the CAR group revealed evident tissue alterations, such as oedema, infiltrates of inflammatory cells and emphysema. These alterations were significantly reduced in the groups treated with LPSF/RA-4 or INDO. Immunohistochemistry revealed an increase in inflammatory markers (COX-2, iNOS, TNF-α and IL-1β) in the lung tissue of the CAR group, whereas the groups treated with LPSF/RA-4 and INDO exhibited significant reductions in such immunomarkers. Western blot analysis revealed an increased expression of COX-2 and IL-1 in the CAR group, which was reduced by treatment with LPSF/RA-4. The present findings demonstrate the potent anti-inflammatory action of the novel derivative thiazolidinedione LPSF/RA-4 in acute lung injury induced by carrageenan.
Bibliography:	http://dx.doi.org/10.1016/j.ejphar.2013.08.033 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-2999 1879-0712
DOI:	10.1016/j.ejphar.2013.08.033