The antipyretic effect of dipyrone is unrelated to inhibition of PGE(2) synthesis in the hypothalamus

Autor(es)

Malvar, David do C. ; Soares, Denis M. ; Fabricio, Aline S. C. ^[1] ; Kanashiro, Alexandre ; Machado, Renes R. ; Figueiredo, Maria J. ; Rae, Giles A. ^[2] ; de Souza, Gloria E. P. ^[3]

Afiliação do(s) autor(es)

^[1] Venice Reg Hosp, ABO Assoc Applicat Biotechnol Oncol, Reg Ctr Study Biol Markers Malignancy, Venice - Italy

^[2] Univ Fed Santa Catarina, Dept Pharmacol, Ctr Biol Sci, Florianopolis, SC - Brazil

^[3] Univ Sao Paulo, Lab Farmacol, Dept Fis & Quim, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: British Journal of Pharmacology; v. 162, n. 6, p. 1401-1409, MAR 2011.
• Citações Web of Science: 21

Resumo

BACKGROUND AND PURPOSE Bacterial lipopolysaccharide (LPS) induces fever through two parallel pathways; one, prostaglandin (PG)-dependent and the other, PG-independent and involving endothelin-1 (ET-1). For a better understanding of the mechanisms by which dipyrone exerts antipyresis, we have investigated its effects on fever and changes in PGE(2) content in plasma, CSF and hypothalamus induced by either LPS or ET-1. EXPERIMENTAL APPROACH Rats were given (i.p.) dipyrone (120 mg center dot kg-1) or indomethacin (2 mg center dot kg-1) 30 min before injection of LPS (5 mu g center dot kg-1, i.v.) or ET-1 (1 pmol, i.c.v.). Rectal temperature was measured by tele-thermometry. PGE(2) levels were determined in the plasma, CSF and hypothalamus by elisa. KEY RESULTS LPS or ET-1 induced fever and increased CSF and hypothalamic PGE(2) levels. Two hours after LPS, indomethacin reduced CSF and hypothalamic PGE(2) but did not inhibit fever, while at 3 h it reduced all three parameters. Three hours after ET-1, indomethacin inhibited the increase in CSF and hypothalamic PGE(2) levels but did not affect fever. Dipyrone abolished both the fever and the increased CSF PGE(2) levels induced by LPS or ET-1 but did not affect the increased hypothalamic PGE(2) levels. Dipyrone also reduced the increase in the venous plasma PGE(2) concentration induced by LPS. CONCLUSIONS AND IMPLICATIONS These findings confirm that PGE(2) does not play a relevant role in ET-1-induced fever. They also demonstrate for the first time that the antipyretic effect of dipyrone was not mechanistically linked to the inhibition of hypothalamic PGE(2) synthesis. (AU)

• Processo FAPESP: 07/04791-1 - Isolamento e caracterização bioquímica da fração responsável pelo efeito pirogênico e nociceptivo presente no veneno do escorpião Tityus serrulatus
• Beneficiário: Glória Emília Petto de Souza
• Modalidade de apoio: Auxílio à Pesquisa - Regular