Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats

Brazilian Journal of Medical and Biological Research

J.s.m. Pasin²  A.p.o. Ferreira¹  A.l.l. Saraiva¹  V. Ratzlaff¹  R. Andrighetto¹  P. Machado¹  S. Marchesan¹  R.a. Zanette¹  H.g. Bonacorso¹  N. Zanatta¹  M.a.p. Martins¹  J. Ferreira¹  C.f. Mello² 

[1] ,Universidade Federal do Rio Grande do Sul Instituto de Ciências Básicas da Saúde Programa de Pós-Graduação em Ciências Biológicas: BioquímicaPorto Alegre RS ,Brasil

关键词: Pyrazole derivatives;    Fever;    Cytokine levels;    Cyclooxygenase;   

DOI  :  10.1590/S0100-879X2010007500139

来源: SciELO

【 摘 要 】

The objective of this study was to determine the effect of eight 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-carboxyamidepyrazoles (TFDPs) on rat body temperature and baker’s yeast-induced fever. TFDPs or vehicle (5% Tween 80 in 0.9% NaCl, 5 mL/kg) were injected subcutaneously and rectal temperature was measured as a function of time in 28-day-old male Wistar rats (N = 5-12 per group). Antipyretic activity was determined in feverish animals injected with baker’s yeast (Saccharomyces cerevisiae suspension, 0.135 mg/kg, 10 mL/kg, ip). 3-Ethyl- and 3-propyl-TFDP (140 and 200 μmol/kg, respectively, 4 h after yeast injection) attenuated baker’s yeast-induced fever by 61 and 82%, respectively. These two effective antipyretics were selected for subsequent analysis of putative mechanisms of action. We then determined the effects on cyclooxygenase-1 and -2 (COX-1 and COX-2) activities on 1,1-diphenyl-2-picrylhydrazyl (DPPH) oxidation in vitro, on tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels and on leukocyte counts in the washes of peritoneal cavities of rats injected with baker’s yeast. While 3-ethyl- and 3-propyl-TFDP did not reduce baker’s yeast-induced increases of IL-1β or TNF-α levels, 3-ethyl-TFDP caused a 42% reduction in peritoneal leukocyte count. 3-Ethyl- and 3-propyl-TFDP did not alter COX-1 or COX-2 activities in vitro, but presented antioxidant activity in the DPPH assay with an IC50 of 39 mM (25-62) and 163 mM (136-196), respectively. The data indicate that mechanisms of action of these two novel antipyretic pyrazole derivatives do not involve the classic inhibition of the COX pathway or pyrogenic cytokine release.

【 授权许可】

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