title: Probucol attenuates overt pain-like behavior and carrageenan-induced inflammatory hyperalgesia and leukocyte recruitment by inhibiting NF-кB activation and cytokine production without antioxidant effects.
abstract: OBJECTIVE
  This study aimed to evaluate the effect of probucol in inflammatory hyperalgesia and leukocyte recruitment in mice.
  
  
  METHODS
  Probucol at 0.3-3 mg/kg was administrated per oral 1 h before inflammatory stimulus.Author: Kindly check and confirm the affiliation 1 have been correctly processed or not and amend if necessary.Thank you. We have corrected affiliation 1. We added the information to the appropriate boxes. However the state and the postal code are in a different order when compared to the other affiliations.
  
  
  METHODS
  Overt pain-like behaviors were determined by the number of abdominal writhings induced by phenyl-p-benzoquinone and acetic acid. Mechanical and thermal hyperalgesia induced by carrageenan were determined using an electronic anesthesiometer and hot plate apparatus, respectively. Leukocyte recruitment was evaluated by direct count or by determination of myeloperoxidase and N-acetylglucosaminidase activities. Antioxidant ability was determined by measurement of GSH levels, ABTS and FRAP assays. Cytokine production and NF-кB activation were evaluated by ELISA. Data were analyzed by ANOVA followed by Tukey's post-hoc. p < 0.05 was considered significant.
  
  
  RESULTS
  Probucol reduced overt pain-like behavior, and carrageenan-induced mechanical and thermal hyperalgesia. These effects were accompanied by reduced leukocyte influx in both paw skin and peritoneum exudate. Probucol did not alter carrageenan-induced tissue antioxidant capacity at anti-inflammatory/analgesic dose. On the other hand, probucol inhibited carrageenan-induced IL-1β, TNF-α and CXCL1 production as well as NF-кB activation.
  
  
  CONCLUSIONS
  Probucol presents analgesic and anti-inflammatory activities by employing mechanisms other than its antioxidant properties. These mechanisms involve targeting of pro-inflammatory cytokines and NF-кB activation.
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Caixa Postal 10.011, Rod. Celso Garcia Cid PR445 km 480, Londrina, Paraná, CEP 86057-970, Brazil.
authors.forename: Amanda Z
authors.initials: AZ
authors.lastname: Zucoloto
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Caixa Postal 10.011, Rod. Celso Garcia Cid PR445 km 480, Londrina, Paraná, CEP 86057-970, Brazil.
authors.forename: Marília F
authors.initials: MF
authors.lastname: Manchope
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Caixa Postal 10.011, Rod. Celso Garcia Cid PR445 km 480, Londrina, Paraná, CEP 86057-970, Brazil.
authors.forename: Larrisa
authors.initials: L
authors.lastname: Staurengo-Ferrari
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, CEP 14049-900, Brazil.
authors.forename: José C
authors.initials: JC
authors.lastname: Alves-Filho
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, CEP 14049-900, Brazil.
authors.forename: Thiago M
authors.initials: TM
authors.lastname: Cunha
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antonio Carlos 6627, Belo Horizonte, Minas Gerais, CEP 31270-901, Brazil.
authors.forename: Maísa M
authors.initials: MM
authors.lastname: Antunes
authors.affiliation: Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Presidente Antonio Carlos 6627, Belo Horizonte, Minas Gerais, CEP 31270-901, Brazil.
authors.forename: Gustavo B
authors.initials: GB
authors.lastname: Menezes
authors.affiliation: Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, CEP 14049-900, Brazil.
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, Londrina, Paraná, CEP 86038-350, Brazil.
authors.forename: Rubia
authors.initials: R
authors.lastname: Casagrande
authors.affiliation: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Caixa Postal 10.011, Rod. Celso Garcia Cid PR445 km 480, Londrina, Paraná, CEP 86057-970, Brazil. waldiceujr@yahoo.com.br.
authors.forename: Waldiceu A
authors.identifier: http://orcid.org/0000-0003-2756-9283
authors.initials: WA
authors.lastname: Verri
mesh_terms: D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D016227:Benzoquinones; D002351:Carrageenan; D016207:Cytokines / Q000276:immunology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D010529:Peritoneal Cavity; D010812:Physical Stimulation; D011341:Probucol / Q000494:pharmacology* / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects / Q000276:immunology
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D016227:Benzoquinones; D016207:Cytokines; D016328:NF-kappa B; C029322:phenylbenzoquinone; D002351:Carrageenan; D011341:Probucol; D019342:Acetic Acid
keywords: Acute inflammation; Carrageenan; Pain; Probucol