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Eur J Pharmacol ; 465(1-2): 183-9, 2003 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-12650848

RESUMO

In a previous work, we investigated the effects of a series of dimethoxy- and trimethoxychalcone derivatives, with various patterns of fluorination, on nitric oxide production in lipopolysaccharide-stimulated murine RAW 264.7 cells. The present study was designed to determine if 2,4,6-trimethoxy-2'-trifluoromethylchalcone (ttCH) could modulate the production of nitric oxide (NO) and/or prostaglandins in vitro and in vivo. On the mouse macrophage cell line RAW 264.7, ttCH inhibited dose-dependently NO and prostaglandin E(2) production, with IC(50) in the micromolar range. This compound had no direct inhibitory effect on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 activities. NO reduction was the consequence of inhibition of the expression of iNOS. This compound also exhibited in vivo an inhibitory behaviour on nitrite and prostaglandin E(2) levels. We have assessed the effect of ttCH in the treatment of acute and chronic inflammatory processes such as the mouse carrageenan paw oedema and the rat adjuvant-induced arthritis. The present study demonstrated that ttCH exerts acute and chronic anti-inflammatory effects that may be related with the inhibition of iNOS expression.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inibidores Enzimáticos/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Animais , Artrite Experimental/diagnóstico por imagem , Artrite Experimental/prevenção & controle , Western Blotting , Carragenina , Linhagem Celular , Ciclo-Oxigenase 2 , Dinoprostona/metabolismo , Edema/induzido quimicamente , Feminino , Membro Posterior/efeitos dos fármacos , Membro Posterior/metabolismo , Membro Posterior/patologia , Inflamação/metabolismo , Inflamação/patologia , Inflamação/prevenção & controle , Isoenzimas/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Prostaglandina-Endoperóxido Sintases/metabolismo , Radiografia , Ratos , Ratos Endogâmicos Lew
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