Daniel C Batista1, Daiany P B Silva2, Iziara F Florentino2, Carina S Cardoso2, Merita P Gonçalves2, Marize C Valadares3, Luciano M Lião4, Germán Sanz5, Boniek G Vaz5, Elson A Costa2, Ricardo Menegatti6. 1. Faculty of Pharmacy, Laboratory of Medicinal Pharmaceutical Chemistry, Federal University of Goiás, Goiânia, GO, Brazil. 2. Department of Pharmacology, ICB, Federal University of Goiás, Campus Samambaia, 314, Goiânia, GO, 74001-970, Brazil. 3. Laboratory of Pharmacology and Cell Toxicology, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO, Brazil. 4. Chemistry Institute, Federal University of Goias, Campus Samambaia, Goiânia, GO, Brazil. 5. Chemistry Institute, Laboratory of Chromatography and Mass Spectrometry-LaCEM, Federal University of Goiás, Goiânia, GO, Brazil. 6. Faculty of Pharmacy, Laboratory of Medicinal Pharmaceutical Chemistry, Federal University of Goiás, Goiânia, GO, Brazil. rm_rj@yahoo.com.
Abstract
AIMS: This study investigates the anti-nociceptive and anti-inflammatory effects of new piperazine compound (LQFM182) as well as the toxicity acute in vitro. MAIN METHODS: 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-α and IL-1β cytokines in pleural exudate. The acute oral systemic toxicity of LQFM182 in mice was evaluated through the neutral red uptake (nru) assay. KEY FINDINGS: 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-1β and TNF-α. Therefore, it was classified in GHS category 300 < LD50 < 2000 mg/kg. SIGNIFICANCE: Reduction of the TNF-α and IL-1β levels.
AIMS: This study investigates the anti-nociceptive and anti-inflammatory effects of new piperazine compound (LQFM182) as well as the toxicity acute in vitro. MAIN METHODS: 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-α and IL-1β cytokines in pleural exudate. The acute oral systemic toxicity of LQFM182 in mice was evaluated through the neutral red uptake (nru) assay. KEY FINDINGS: 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-1β and TNF-α. Therefore, it was classified in GHS category 300 < LD50 < 2000 mg/kg. SIGNIFICANCE: Reduction of the TNF-α and IL-1β levels.
Authors: David do Carmo Malvar; Raquel Teixeira Ferreira; Raphael Andrade de Castro; Ligia Lins de Castro; Antonio Carlos Carreira Freitas; Elson Alves Costa; Iziara Ferreira Florentino; João Carlos Martins Mafra; Glória Emília Petto de Souza; Frederico Argollo Vanderlinde Journal: Life Sci Date: 2013-12-17 Impact factor: 5.037
Authors: Ferdinando Nicoletti; Dominick L Auci; Katia Mangano; Jaime Flores-Riveros; Sonia Villegas; James M Frincke; Christopher L Reading; Halina Offner Journal: Autoimmune Dis Date: 2010-05-18