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(Referência obtida automaticamente do Google Scholar, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Reduction of inflammation in rats by diazepam: tolerance development

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Autor(es):
Lazzarini‚ R. ; Malucelli‚ B.E. ; Muscará‚ M.N. ; de Nucci‚ G. ; Palermo-Neto‚ J.
Número total de Autores: 5
Tipo de documento: Artigo Científico
Fonte: Life Sciences; v. 72, n. 21, p. 2361-2368, 2003.
Resumo

High doses of diazepam (10-20 mg/kg) were shown to reduce the volume of acute carrageenan-induced inflammatory paw edema in rats. This effect was not observed after adrenalectomy or long-term use of similar doses of diazepam. The present experiment was undertaken to analyze the effects of long-term (21 daily injections) treatment with diazepam (10 mg/kg) on both carrageenan-induced paw edema (CIPE) and corticosterone serum levels. For comparison, the effects of a single and acute 10 mg/kg dose of diazepam were also analyzed. Results showed that: 1-long-term diazepam treatment induced no changes in CIPE values and corticosterone serum levels; 2- acute diazepam treatment reduced CIPE values and increased corticosterone serum levels; 3- the plasmatic levels of diazepam measured 1 hour after the single treatment or 1 hour after the last dose of long-term diazepam administration were not different. These results indicate the development of tolerance to diazepam effects on both CIPE and corticosterone serum levels and suggest a relevant role for corticosterone on diazepam-induced inhibition of acute inflammation. Data were discussed in the light of peripheral benzodiazepine receptor site (PBR) activation within adrenal gland cells by diazepam, thereby increasing the serum levels of corticosterone and thus reducing CIPE. Possible actions of diazepam on HPA axis activity and/or on cytokine network were also discussed. (C) 2003 Elsevier Science Inc. All rights reserved. (AU)

Processo FAPESP: 99/04228-7 - Neuroimunomodulação: efeito do estresse e de fármacos com ação no sistema nervoso central sobre a resposta imune/inflamatória
Beneficiário:João Palermo Neto
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 99/04128-2 - O Diazepam e a resposta inflamatória induzida pela carragenina em ratos: parte II: mecanismo de ação
Beneficiário:Ricardo Lazzarini
Modalidade de apoio: Bolsas no Brasil - Doutorado