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 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

Distribution and isotopic composition of lead in bottom sediments from the hydrographic system of Belém, Pará (western margin of Guajará Bay and Carnapijó River)

ABSTRACT: This study first aimed to evaluate the effect of human activities on the distribution of lead within the estuarine system of Belém, Pará. This was achieved by studying the concentration and isotopic signature of Pb in bottom sediments from the western margin of Guajará Bay and from Carnapijó River, an area removed from the influence of the city of Belém. Secondly, the contribution of suspended matter in the transportation of anthropogenic Pb in Guajará Bay was evaluated. Third, the content and background isotopic signature of Pb in the hydrographic system of Belém was determined. Isotopic signatures of sediments from the western margin of Guajará Bay confirm an anthropogenic contribution of Pb throughout the entire bay. The Pb accumulation process has become more efficient over the last 10 years, and this can be attributed to the rapid population growth of Belém city. Sediments in Carnapijó River are not affected by human activities, and the average concentration values (Pb = 19.6 ± 3.7 mg kg-1) and isotopic signatures (206Pb/207Pb = 1.196 ± 0.004) confirm the background Pb values previously proposed for the river system in the Belém region. The isotopic signatures of suspended matter on the eastern (206Pb/207Pb = 1.188) and western (206Pb/207Pb = 1.174) margins of Guajará Bay show that suspended matter is an efficient Pb transportation mechanism of domestic and industrial wastewater from Belém to the western margin of the Bay due to tidal effects at the confluence with Guamá River