Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats
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...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Associação Brasileira de Divulgação Científica
2010-12-01
|
| Series: | Brazilian Journal of Medical and Biological Research |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010001200009 |
| _version_ | 1819038531206512640 |
|---|---|
| author | J.S.M. Pasin A.P.O. Ferreira A.L.L. Saraiva V. Ratzlaff R. Andrighetto P. Machado S. Marchesan R.A. Zanette H.G. Bonacorso N. Zanatta M.A.P. Martins J. Ferreira C.F. Mello |
| author_facet | J.S.M. Pasin A.P.O. Ferreira A.L.L. Saraiva V. Ratzlaff R. Andrighetto P. Machado S. Marchesan R.A. Zanette H.G. Bonacorso N. Zanatta M.A.P. Martins J. Ferreira C.F. Mello |
| author_sort | J.S.M. Pasin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T08:38:47Z |
| format | Article |
| id | doaj.art-b831d50e6f594a02866f1933244c5277 |
| institution | Directory Open Access Journal |
| issn | 0100-879X 1414-431X |
| language | English |
| last_indexed | 2024-12-21T08:38:47Z |
| publishDate | 2010-12-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-b831d50e6f594a02866f1933244c52772022-12-21T19:09:59ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X1414-431X2010-12-01431211931202Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in ratsJ.S.M. PasinA.P.O. FerreiraA.L.L. SaraivaV. RatzlaffR. AndrighettoP. MachadoS. MarchesanR.A. ZanetteH.G. BonacorsoN. ZanattaM.A.P. MartinsJ. FerreiraC.F. MelloThe 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010001200009Pyrazole derivativesFeverCytokine levelsCyclooxygenase |
| spellingShingle | J.S.M. Pasin A.P.O. Ferreira A.L.L. Saraiva V. Ratzlaff R. Andrighetto P. Machado S. Marchesan R.A. Zanette H.G. Bonacorso N. Zanatta M.A.P. Martins J. Ferreira C.F. Mello Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats Brazilian Journal of Medical and Biological Research Pyrazole derivatives Fever Cytokine levels Cyclooxygenase |
| title | Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats |
| title_full | Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats |
| title_fullStr | Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats |
| title_full_unstemmed | Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats |
| title_short | Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats |
| title_sort | antipyretic and antioxidant activities of 5 trifluoromethyl 4 5 dihydro 1h pyrazoles in rats |
| topic | Pyrazole derivatives Fever Cytokine levels Cyclooxygenase |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010001200009 |
| work_keys_str_mv | AT jsmpasin antipyreticandantioxidantactivitiesof5trifluoromethyl45dihydro1hpyrazolesinrats AT apoferreira antipyreticandantioxidantactivitiesof5trifluoromethyl45dihydro1hpyrazolesinrats AT allsaraiva antipyreticandantioxidantactivitiesof5trifluoromethyl45dihydro1hpyrazolesinrats AT vratzlaff antipyreticandantioxidantactivitiesof5trifluoromethyl45dihydro1hpyrazolesinrats AT randrighetto antipyreticandantioxidantactivitiesof5trifluoromethyl45dihydro1hpyrazolesinrats AT pmachado antipyreticandantioxidantactivitiesof5trifluoromethyl45dihydro1hpyrazolesinrats AT smarchesan antipyreticandantioxidantactivitiesof5trifluoromethyl45dihydro1hpyrazolesinrats AT razanette antipyreticandantioxidantactivitiesof5trifluoromethyl45dihydro1hpyrazolesinrats AT hgbonacorso antipyreticandantioxidantactivitiesof5trifluoromethyl45dihydro1hpyrazolesinrats AT nzanatta antipyreticandantioxidantactivitiesof5trifluoromethyl45dihydro1hpyrazolesinrats AT mapmartins antipyreticandantioxidantactivitiesof5trifluoromethyl45dihydro1hpyrazolesinrats AT jferreira antipyreticandantioxidantactivitiesof5trifluoromethyl45dihydro1hpyrazolesinrats AT cfmello antipyreticandantioxidantactivitiesof5trifluoromethyl45dihydro1hpyrazolesinrats |