Inflammation Research

, Volume 66, Issue 7, pp 591–602 | Cite as

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

  • Amanda Z. Zucoloto
  • Marília F. Manchope
  • Larrisa Staurengo-Ferrari
  • José C. Alves-Filho
  • Thiago M. Cunha
  • Maísa M. Antunes
  • Gustavo B. Menezes
  • Fernando Q. Cunha
  • Rubia Casagrande
  • Waldiceu A. VerriJr.Email author
Original Research Paper


Objective and design

This study aimed to evaluate the effect of probucol in inflammatory hyperalgesia and leukocyte recruitment in mice.


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.


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.


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.


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.


Probucol Carrageenan Pain Acute inflammation 



The authors would like to thank the methodological support of Sandra S. Mizokami, the technical support of Giuliana Bertozi Francisco and the financial support of Conselho Nacional do Desenvolvimento Científico e Tecnológico (CNPq), Coordenação do Aperfeiçoamento de Pessoal de Nível Superior (CAPES), São Paulo Research Foundation under Grant agreements No. 2011/19670-0 (Thematic project) and 2013/08216-2 (Center for Research in Inflammatory Disease), Ministério da Ciência, Tecnologia e Inovação (MCTI), Secretaria da Ciência, Tecnologia e Inovação (SETI), Fundação Araucária and Parana State Government.


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Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  • Amanda Z. Zucoloto
    • 1
  • Marília F. Manchope
    • 1
  • Larrisa Staurengo-Ferrari
    • 1
  • José C. Alves-Filho
    • 2
  • Thiago M. Cunha
    • 2
  • Maísa M. Antunes
    • 3
  • Gustavo B. Menezes
    • 3
  • Fernando Q. Cunha
    • 2
  • Rubia Casagrande
    • 4
  • Waldiceu A. VerriJr.
    • 1
    Email author
  1. 1.Departamento de Ciências Patológicas, Centro de Ciências BiológicasUniversidade Estadual de LondrinaLondrinaBrazil
  2. 2.Department of Pharmacology, Ribeirão Preto Medical SchoolUniversity of São PauloRibeirão PretoBrazil
  3. 3.Departamento de Morfologia, Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteBrazil
  4. 4.Departamento de Ciências Farmacêuticas, Centro de Ciências da SaúdeUniversidade Estadual de LondrinaLondrinaBrazil

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