Diazepam decreases leukocyte-endothelium interactions in situ

Autor(es)

Lazzarini, R. ; Sakai, M. ; Costa-Pinto, F. A. ; Palermo-Neto, J. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Vet & Zootecnia, Dept Pathol, Neuroimmunomodulat Res Grp, Lab Farmacol Aplicada & Toxicol, Sch Vet Med & Ani, BR-05508000 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Immunopharmacology and Immunotoxicology; v. 32, n. 3, p. 402-409, SEP 2010.
• Citações Web of Science: 9

Resumo

High doses of diazepam reduce the inflammatory paw edema in rats. This effect was attributed to an action of diazepam on the Translocator Protein (TSPO). We evaluated the effects of diazepam (10 mg/kg, intraperitoneally) on leukocyte rolling and migration. In carrageenan-induced acute inflammation, diazepam decreased the interaction of leukocytes with endothelial cells (rolling) and the number of leukocytes in the mesentery (migration). RU486 (antagonist of glucocorticoid receptors) reduced the effects of diazepam on leukocyte rolling and migration, suggesting a participation of endogenous corticosteroids. We also showed that the effects of diazepam on leukocyte-endothelium interactions are mediated by nitric oxide (NO), since prior treatment with l-arginine (precursor of NO) partially precludes the inhibitory effects of diazepam; conversely, pretreatment with L-NAME (false substrate of the NO synthase) somewhat potentiates the effects of diazepam. The pathways that underlie the effects of diazepam remain to be further elucidated, but we believe that both local and systemic mechanisms may overlap to explain the influence of diazepam on leukocyte-endothelium interactions. (AU)

• Processo FAPESP: 05/52916-2 - Os efeitos de diazepam na resposta inflamatória em ratos: avaliação pelo método de microcirculação in situ
• Beneficiário: Ricardo Lazzarini
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 04/14128-0 - Neuroimunomodulação: efeitos do estresse e de citocinas nas relações bidirecionais entre os sistemas nervosos central e imune
• Beneficiário: João Palermo Neto
• Modalidade de apoio: Auxílio à Pesquisa - Temático