title: Curcumin inhibits superoxide anion-induced pain-like behavior and leukocyte recruitment by increasing Nrf2 expression and reducing NF-κB activation.
abstract: OBJECTIVE
  This study aimed at evaluating the activity of curcumin in superoxide anion-induced pain-like behavior and leukocyte recruitment in mice.
  
  
  METHODS
  Administration of curcumin 10 mg/kg subcutaneously 1 h before stimulus.
  
  
  METHODS
  KO2 was used as superoxide anion donor. Overt pain-like behaviors were determined by the number of abdominal writhings, paw flinches and time spent licking the paw. Mechanical and thermal hyperalgesia were determined using an electronic anesthesiometer and hot plate, respectively. Cytokine concentration and NF-κB activity were determined by ELISA, antioxidant effect by nitrobluetretrazolium assay and ABTS radical scavenging ability. Myeloperoxidase activity was measured by colorimetric assay. The Nrf2, heme oxygenase-1 (HO-1) and gp91phox mRNA expression was determined by quantitative PCR. Data were analyzed by ANOVA followed by Tukey's post hoc and considered significant when p<0.05.
  
  
  RESULTS
  Curcumin inhibited superoxide anion-induced overt pain-like behaviors as well as mechanical and thermal hyperalgesia. Curcumin also inhibited superoxide anion-induced leukocyte recruitment in the peritoneal cavity and in the paw skin inhibited myeloperoxidase activity, oxidative stress, IL-1β and TNF-α production and NF-κB activation as well as enhanced IL-10 production, and HO-1 and Nrf2 mRNA expression.
  
  
  CONCLUSIONS
  Curcumin inhibits superoxide anion-induced inflammatory pain-like behaviors and leukocyte recruitment by targeting inflammatory molecules and oxidative stress; and inducing antioxidant and anti-inflammatory pathways.
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86057-970, Londrina, Paraná, Cx Postal 10.011, Brasil.
authors.forename: Victor
authors.initials: V
authors.lastname: Fattori
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86057-970, Londrina, Paraná, Cx Postal 10.011, Brasil.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Pinho-Ribeiro
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86057-970, Londrina, Paraná, Cx Postal 10.011, Brasil.
authors.forename: Sergio M
authors.initials: SM
authors.lastname: Borghi
authors.affiliation: Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, CEP 14049-900, Ribeirão Preto, São Paulo, Brasil.
authors.forename: José C
authors.initials: JC
authors.lastname: Alves-Filho
authors.affiliation: Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, CEP 14049-900, Ribeirão Preto, São Paulo, Brasil.
authors.forename: Thiago M
authors.initials: TM
authors.lastname: Cunha
authors.affiliation: Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, CEP 14049-900, Ribeirão Preto, São Paulo, Brasil.
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.affiliation: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Estadual de Londrina, Av. Robert Koch 60, CEP 86038-350, Londrina, Paraná, Brasil.
authors.forename: Rubia
authors.initials: R
authors.lastname: Casagrande
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, CEP 86057-970, Londrina, Paraná, Cx Postal 10.011, Brasil. waldiceujr@yahoo.com.br.
authors.forename: Waldiceu A
authors.initials: WA
authors.lastname: Verri
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control; D007279:Injections, Subcutaneous; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000737:chemistry; D010146:Pain / Q000139:chemically induced / Q000523:psychology*; D017680:Potassium Compounds / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013481:Superoxides / Q000037:antagonists & inhibitors* / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D008562:Membrane Glycoproteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D016877:Oxidants; D010087:Oxides; D017680:Potassium Compounds; D012333:RNA, Messenger; D013481:Superoxides; C068440:potassium oxide; D051547:Heme Oxygenase-1; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D003474:Curcumin
keywords: Curcumin; IL-10; NF-κB; Nrf2; Pain; Superoxide anion