title: Reduction of carrageenan-induced acute pulmonary inflammation in mice by novel thiazolidinedione derivative LPSF/RA-4.
abstract: 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 (60 μmol/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.
authors.affiliation: Laboratório de Ultraestrutura, Instituto Aggeu Magalhães, FIOCRUZ, Recife, Brazil. Electronic address: karlapsb@gmail.com.
authors.forename: Karla P S
authors.initials: KP
authors.lastname: Barbosa
authors.forename: Laise A M
authors.initials: LA
authors.lastname: Santos
authors.forename: Edlene L
authors.initials: EL
authors.lastname: Ribeiro
authors.forename: Ingrid T
authors.initials: IT
authors.lastname: Fragoso
authors.forename: Sura W S
authors.initials: SW
authors.lastname: Rocha
authors.forename: Ana K S
authors.initials: AK
authors.lastname: Nunes
authors.forename: Maria E R
authors.initials: ME
authors.lastname: França
authors.forename: Bruna S
authors.initials: BS
authors.lastname: Silva
authors.forename: Amanda K S E
authors.initials: AK
authors.lastname: Silva
authors.forename: Mariana A M
authors.initials: MA
authors.lastname: Donato
authors.forename: Fabiana O S
authors.initials: FO
authors.lastname: Gomes
authors.forename: Teresinha G
authors.initials: TG
authors.lastname: Silva
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Pitta
authors.forename: Marina R
authors.initials: MR
authors.lastname: Pitta
authors.forename: Maria C A
authors.initials: MC
authors.lastname: Lima
authors.forename: Flávia D T
authors.initials: FD
authors.lastname: Uchôa
authors.forename: Suely L
authors.initials: SL
authors.lastname: Galdino
authors.forename: Christina A
authors.initials: CA
authors.lastname: Peixoto
mesh_terms: D000208:Acute Disease; D000818:Animals; D002351:Carrageenan / Q000009:adverse effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000378:metabolism; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy; D011014:Pneumonia / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000235:genetics; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C000588773:3-benzyl-5-(1H-indol-3-ylmethylene)-thiazolidine-2,4-dione; D007211:Indoles; D018836:Inflammation Mediators; D045162:Thiazolidinediones; D009569:Nitric Oxide; D002351:Carrageenan; C089946:2,4-thiazolidinedione
keywords: Acute lung injury; Peroxisome proliferator-activated receptor; Pleurisy; Thiazolidinedione