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Naringenin mitigates titanium dioxide (TiO2)-induced chronic arthritis in mice: role of oxidative stress, cytokines, and NFκB

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Abstract

Objective

To evaluate the effect and mechanisms of naringenin in TiO2-induced chronic arthritis in mice, a model resembling prosthesis and implant inflammation.

Treatment

Flavonoids are antioxidant and anti-inflammatory molecules with important anti-inflammatory effect. Mice were daily treated with the flavonoid naringenin (16.7–150 mg/kg, orally) for 30 days starting 24 h after intra-articular knee injection of 3 mg of TiO2.

Methods

TiO2-induced arthritis resembles cases of aseptic inflammation induced by prosthesis and/or implants. Mice were stimulated with 3 mg of TiO2 and after 24 h mice started to be treated with naringenin. The disease phenotype, treatment toxicity, histopathological damage, oxidative stress, cytokine expression and NFκB were evaluated after 30 days of treatment.

Results

Naringenin inhibited TiO2-induced mechanical hyperalgesia (96%), edema (77%) and leukocyte recruitment (74%) without inducing toxicity. Naringenin inhibited histopathological index (HE, 49%), cartilage damage (Toluidine blue tibial staining 49%, and proteoglycan 98%), and bone resorption (TRAP-stained 73%). These effects were accompanied by inhibition of oxidative stress (gp91phox 93%, NBT 83%, and TBARS 41%) cytokine mRNA expression (IL-33 82%, TNFα 76%, pro-IL-1β 100%, and IL-6 61%), and NFκB activation (100%).

Conclusion

Naringenin ameliorates TiO2-induced chronic arthritis inducing analgesic and anti-inflammatory responses with improvement in the histopathological index, cartilage damage, and bone resorption.

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Acknowledgements

We thank M.R.F.D.P., A.Z.Z., and M.M.B for the technical support and T.H.Z for the support in the Adobe Illustrator. This study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), São Paulo research Foundation (FAPESP) under grant agreements number 2011/19670-0 (Thematic project) and 2013/08216-2 (Center for Research in Inflammatory Disease-CRID), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; Finance Code 001), and Programa de Pesquisa para o SUS (PPSUS) grant supported by Ministério da Ciência, Tecnologia e Inovação (MCTI), Secretaria da Ciência, Tecnologia e Ensino Superior (SETI), Decit/SCTIE/MS through CNPq with the support of Fundação Araucária and Secretaria da Saúde do Estado do Paraná (SESA-PR), and Parana State Government (Brazil).

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  1. Marília F. Manchope, Victor Fattori, Sandra S. Mizokami & Waldiceu A. Verri Jr.

    Present address: Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid Km480 PR445, Cx Postal 10.011, Londrina, Paraná, CEP 86057-970, Brazil

Authors and Affiliations

  1. Departamento de Ciências Farmacêuticas, Centro de Ciências de Saúde, Universidade Estadual de Londrina, Londrina, Brazil

    Nayara A. Artero & Rubia Casagrande

  2. Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil

    Dimitrius L. Pitol & João P. M. Issa

  3. Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil

    Sandra Y. Fukada

  4. Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil

    Thiago M. Cunha, José C. Alves-Filho & Fernando Q. Cunha

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  1. Marília F. Manchope
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Manchope, M.F., Artero, N.A., Fattori, V. et al. Naringenin mitigates titanium dioxide (TiO2)-induced chronic arthritis in mice: role of oxidative stress, cytokines, and NFκB. Inflamm. Res. 67, 997–1012 (2018). https://doi.org/10.1007/s00011-018-1195-y

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  • DOI: https://doi.org/10.1007/s00011-018-1195-y

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