title: Nicorandil inhibits neutrophil recruitment in carrageenan-induced experimental pleurisy in mice.
abstract: Nicorandil is a drug characterized by the coupling of a nitric oxide (NO) donor to nicotinamide. We have previously demonstrated that nicotinamide exhibits activity in different models of pain and inflammation. Now, we investigated the effects induced by per os (p.o.) administration of nicorandil (25, 50 or 100mg/Kg) on neutrophil recruitment in a carrageenan-induced model of pleurisy in mice. Effects induced by nicorandil (100mg/kg) were compared with those induced by equimolar doses of nicotinamide (58mg/kg) and N-(2-hydroxyethyl)-nicotinamide (NHN; 79mg/kg). We also investigated whether effects on the production of inflammatory mediators play a role in the activity of nicorandil. P.o. nicorandil, 0.5h before and 1h after the i.pl. injection of carrageenan, reduced neutrophil recruitment. However, equimolar doses of nicotinamide or NHN failed to induce such effect. Single treatment (previous or late) with nicorandil (100mg/Kg, p.o.) also reduced neutrophils recruitment, although to a lesser extent when compared to the double treatment. Nicorandil reduced the concentrations of interleukin-1β, CXCL-1 and prostaglandin E2 in the pleural exudate. Concluding, we demonstrated the activity of nicorandil in a model of pleurisy induced by carrageenan. This activity was characterized by reduction of the neutrophil accumulation and inhibition of production of inflammatory mediators. The effects induced by nicorandil on the leukocytes recruitment and production of inflammatory mediators contribute to a better understanding of its clinical benefits and indicate that these benefits may be due to its vasodilating and anti-inflammatory activities.
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Tamires C
authors.initials: TC
authors.lastname: Matsui
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Giovanna M E
authors.initials: GM
authors.lastname: Coura
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Ivo S F
authors.initials: IS
authors.lastname: Melo
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Carla R A
authors.initials: CR
authors.lastname: Batista
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Paulo Sérgio A
authors.initials: PS
authors.lastname: Augusto
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Godin
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Débora P
authors.initials: DP
authors.lastname: Araújo
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Isabela C
authors.initials: IC
authors.lastname: César
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Lucas S
authors.initials: LS
authors.lastname: Ribeiro
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Danielle G
authors.initials: DG
authors.lastname: Souza
authors.affiliation: Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Klein
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Ângelo
authors.initials: Â
authors.lastname: de Fátima
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Renes R
authors.initials: RR
authors.lastname: Machado
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil. Electronic address: marciocoelhobh@yahoo.com.br.
authors.forename: Márcio M
authors.initials: MM
authors.lastname: Coelho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002351:Carrageenan / Q000009:adverse effects*; D016207:Cytokines / Q000096:biosynthesis; D015777:Eicosanoids / Q000096:biosynthesis; D005260:Female; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects*; D020108:Nicorandil / Q000494:pharmacology* / Q000627:therapeutic use; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D015777:Eicosanoids; D020108:Nicorandil; D002351:Carrageenan
keywords: Cytokines; Inflammation; Neutrophils; Nicorandil; Nicotinamide; Prostaglandin E(2)