Abstract
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.
Highlights
Fever is a regulated increase of body core temperature characterized by an increase thermoregulatory set point, which results from the interaction of the central nervous and immune systems [1]
Since peritoneal leukocyte migration is important for fever development [17], we investigated whether compounds 3Et-TFDP and 3Pr-TFDP altered number of leukocytes in the peritoneal cavity
We showed that a series of TFDPs decreased TR with time and attenuated baker’s yeastinduced fever in young rats
Summary
Fever is a regulated increase of body core temperature characterized by an increase thermoregulatory set point, which results from the interaction of the central nervous and immune systems [1]. There is evidence supporting the idea that fever enhances host defenses, some studies have suggested that raising core temperature to the febrile range may be harmful. In clinical situations in which fever-associated risks outweigh benefits, antipyretic treatment is indicated [3]. Pyrazoles constitute an important group of organic compounds that have been extensively studied due to their numerous biological activities. Dipyrone ( known as metamizole) is a potent antipyretic and analgesic pyrazole derivative, with little anti-inflammatory activity [4], that is used in several countries.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
