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Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-γ, reduces acute inflammation

Cuzzocrea, Salvatore ; Pisano, Barbara ; Dugo, Laura ; Ianaro, Angela ; Maffia, Pasquale ; Patel, Nimesh S.A. ; Di Paola, Rosanna ; Ialenti, Armando ; Genovese, Tiziana ; Chatterjee, Prabal K. ; Di Rosa, Massimo ; Caputi, Achille P. ; Thiemermann, Christoph

European journal of pharmacology, 2004, Vol.483 (1), p.79-93 [Periódico revisado por pares]

Amsterdam: Elsevier B.V

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Título:
Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-γ, reduces acute inflammation
Autor: Cuzzocrea, Salvatore ; Pisano, Barbara ; Dugo, Laura ; Ianaro, Angela ; Maffia, Pasquale ; Patel, Nimesh S.A. ; Di Paola, Rosanna ; Ialenti, Armando ; Genovese, Tiziana ; Chatterjee, Prabal K. ; Di Rosa, Massimo ; Caputi, Achille P. ; Thiemermann, Christoph
Assuntos: Animals ; Anti-Inflammatory Agents ; Biological and medical sciences ; Carrageenan ; Cyclooxygenase 2 ; Cytokines - biosynthesis ; Dinoprostone - metabolism ; Edema - chemically induced ; Edema - pathology ; Edema - prevention & control ; Exudates and Transudates - metabolism ; ICAM-1 (intercellular adhesion molecule-1) ; Immunohistochemistry ; Inflammation, acute ; iNOS (nitric oxide synthase inducible) ; Isoenzymes - biosynthesis ; Lipid Peroxidation - drug effects ; Lung - pathology ; Male ; Medical sciences ; Neutrophil Infiltration - drug effects ; Nitrates - metabolism ; Nitric Oxide Synthase - biosynthesis ; Nitric Oxide Synthase Type II ; Nitrites - metabolism ; Peroxidase - metabolism ; Pharmacology. Drug treatments ; Pleurisy - chemically induced ; Pleurisy - pathology ; Pleurisy - prevention & control ; Poly(ADP-ribose) Polymerases - metabolism ; PPAR (peroxisome proliferator-activated receptor) ; Prostaglandin-Endoperoxide Synthases - biosynthesis ; Rats ; Rats, Sprague-Dawley ; Receptors, Cytoplasmic and Nuclear - agonists ; Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors ; Rosiglitazone ; Thiazolidinediones - antagonists & inhibitors ; Thiazolidinediones - pharmacology ; Transcription Factors - agonists ; Transcription Factors - antagonists & inhibitors ; Tyrosine - metabolism
É parte de: European journal of pharmacology, 2004, Vol.483 (1), p.79-93
Descrição: Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid and thyroid hormone receptors. The PPAR-γ receptor subtype appears to play a pivotal role in the regulation of cellular proliferation and inflammation. The thiazolidinedione rosiglitazone (Avandia) is a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, that was recently approved by the Food and Drug Administration for treatment of type II diabetes mellitus. In the present study, we have investigated the effects of rosiglitazone in animal models of acute inflammation (carrageenan-induced paw oedema and carrageenan-induced pleurisy). We report here for the first time that rosiglitazone (given at 1, 3 or 10 mg/kg i.p. concomitantly with carrageenan injection in the paw oedema model, or at 3, 10 or 30 mg/kg i.p. 15 min before carrageenan administration in the pleurisy model) exerts potent anti-inflammatory effects (e.g. inhibition of paw oedema, pleural exudate formation, mononuclear cell infiltration and histological injury) in vivo. Furthermore, rosiglitazone reduced: (1) the increase in the staining (immunohistochemistry) for nitrotyrosine and poly (ADP-ribose) polymerase (PARP), (2) the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), intercellular adhesion molecules-1 (ICAM-1) and P-selectin in the lungs of carrageenan-treated rats. In order to elucidate whether the protective effect of rosiglitazone is related to activation of the PPAR-γ receptor, we also investigated the effect of a PPAR-γ antagonist, bisphenol A diglycidyl ether (BADGE), on the protective effects of rosiglitazone. BADGE (30 mg/kg i.p.) administered 30 min prior to treatment with rosiglitazone significantly antagonized the effect of the PPAR-γ agonist and thus abolished the anti-inflammatory effects of rosiglitazone. We propose that rosiglitazone and other potent PPAR-γ agonists may be useful in the therapy of inflammation.
Editor: Amsterdam: Elsevier B.V
Idioma: Inglês

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Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-γ, reduces acute inflammation

Cuzzocrea, Salvatore ; Pisano, Barbara ; Dugo, Laura ; Ianaro, Angela ; Maffia, Pasquale ; Patel, Nimesh S.A. ; Di Paola, Rosanna ; Ialenti, Armando ; Genovese, Tiziana ; Chatterjee, Prabal K. ; Di Rosa, Massimo ; Caputi, Achille P. ; Thiemermann, Christoph

Amsterdam: Elsevier B.V

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