RESUMO
Mouse pleurisy induced by carrageenan is used to determine the mechanism of anti-inflammatory action of 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2-H-1,4-benzodiazepin-2 (Ro5-4864). Pre-treatment with Ro5-4864 inhibits different inflammatory parameters, such as neutrophil influx, MPO activity and NO levels in the early phase (4 h), as well as mononuclear cells and ADA activity in the late phase (48 h) of pleurisy. dl-Aminoglutethimide, inhibitor of steroidal synthesis, reverted the effect of Ro5-4864 on these different inflammatory parameters. Our results suggest that anti-inflammatory action of Ro5-4864 may be partly due to its capacity to inhibit leukocyte migration, as well as leukocyte activation and formation of NO by a mechanism dependent on glucocorticoids.
Assuntos
Anti-Inflamatórios/uso terapêutico , Benzodiazepinonas/uso terapêutico , Carragenina/toxicidade , Glucocorticoides/uso terapêutico , Pleurisia/tratamento farmacológico , Adenosina Desaminase/metabolismo , Adrenérgicos/farmacologia , Aminoglutetimida/farmacologia , Animais , Movimento Celular , Quimiotaxia de Leucócito , Feminino , Masculino , Camundongos , Neutrófilos/metabolismo , Óxido Nítrico/metabolismo , Peroxidase/metabolismo , Pleurisia/induzido quimicamente , Pleurisia/metabolismoRESUMO
BACKGROUND: Studies on peripheral benzodiazepine receptor function have yielded a diverse list of activities of which the anti-inflammatory effects need to be further examined. AIMS: To evaluate the role of steroids, nitric oxide and adenosine-deaminase in the anti-inflammatory effect of PK11195. METHODS: Pleurisy was induced by intrapleural injection of carrageenan in mice pre-treated or not with PK11195. Leukocytes, exudation, adenosine-deaminase (ADA) activity and nitric oxide (NO) level were measured. Steroid involvement was evaluated by pre-treatment with D,L-aminogluthetimide before PK11195. RESULTS: Leukocytes, exudation and NO levels were reduced by PK11195 in the early (4 h) phase. In the late (48 h) phase, PK11195 decreased leukocytes and ADA activity. D,L-aminogluthetimide reversed the effect of PK11195 on exudate (4 h), as well as total and differential leukocytes and NO levels (48 h). CONCLUSIONS: Steroids, NO and ADA are implicated in the anti-inflammatory action of PK11195.