Anti-inflammatory effect of a new piperazine derivative: (4-methylpiperazin-1-yl)(1-phenyl-1H-pyrazol-4-yl)methanone

被引:19
作者
Batista, Daniel C. [1 ]
Silva, Daiany P. B. [2 ]
Florentino, Iziara F. [2 ]
Cardoso, Carina S. [2 ]
Goncalves, Merita P. [2 ]
Valadares, Marize C. [3 ]
Liao, Luciano M. [4 ]
Sanz, German [5 ]
Vaz, Boniek G. [5 ]
Costa, Elson A. [2 ]
Menegatti, Ricardo [1 ]
机构
[1] Univ Fed Goias, Fac Pharm, Lab Med Pharmaceut Chem, Goiania, Go, Brazil
[2] Univ Fed Goias, ICB, Dept Pharmacol, Campus Samambaia 314, BR-74001970 Goiania, Go, Brazil
[3] Univ Fed Goias, Fac Pharm, Lab Pharmacol & Cell Toxicol, Goiania, Go, Brazil
[4] Univ Fed Goias, Chem Inst, Campus Samambaia, Goiania, Go, Brazil
[5] Univ Fed Goias, Chem Inst, Lab Chromatog & Mass Spectrometry LaCEM, Goiania, Go, Brazil
关键词
Anti-inflammatory; N-arylheterocycles; IL-1; beta; TNF-alpha; HISTAMINE H-4 RECEPTOR; ANTI-INFLAMMATORY DRUGS; NF-KAPPA-B; FORMALIN TEST; SIGNALING PATHWAY; ACETIC-ACID; CARRAGEENAN; RAT; PAIN; 4-NEROLIDYLCATECHOL;
D O I
10.1007/s10787-017-0390-8
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
This study investigates the anti-nociceptive and anti-inflammatory effects of new piperazine compound (LQFM182) as well as the toxicity acute in vitro. To evaluate the anti-nociceptive activity, the acetic acid-induced abdominal writhing test, tail flick test and formalin-induced pain test were used. The anti-inflammatory activity was evaluated using the models of paw oedema and pleurisy induced by carrageenan and some inflammatory parameters were evaluated, including cell migration, myeloperoxidase enzyme activity and the levels of TNF-alpha and IL-1 beta cytokines in pleural exudate. The acute oral systemic toxicity of LQFM182 in mice was evaluated through the neutral red uptake (nru) assay. LQFM182 (50, 100 or 200 mg/kg, p.o.) decreased the number of writhings induced by acetic acid in a dose-dependent manner, and an intermediate dose (100 mg/kg, p.o.) reduced the paw licking time of animals in the second phase of the formalin test. Furthermore, LQFM182 (100 mg/kg, p.o.) reduced oedema formation at all hours of the paw oedema induced by carrageenan test and in pleurisy test reduced cell migration from the reduction of polymorphonuclear cells, myeloperoxidase enzyme activity and the levels of pro-inflammatory cytokines IL-1 beta and TNF-alpha. Therefore, it was classified in GHS category 300 < LD50 < 2000 mg/kg. Reduction of the TNF-alpha and IL-1 beta levels.
引用
收藏
页码:217 / 226
页数:10
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