The flavonoid quercetin inhibits titanium dioxide (TiO 2 )-induced chronic arthritis in mice.

Autor: Borghi SM; Department of Pathology, Center of Biological Sciences, State University of Londrina, 86057-970, Londrina, Paraná, Brazil., Mizokami SS; Department of Pathology, Center of Biological Sciences, State University of Londrina, 86057-970, Londrina, Paraná, Brazil., Pinho-Ribeiro FA; Department of Pathology, Center of Biological Sciences, State University of Londrina, 86057-970, Londrina, Paraná, Brazil., Fattori V; Department of Pathology, Center of Biological Sciences, State University of Londrina, 86057-970, Londrina, Paraná, Brazil., Crespigio J; Department of Pathology, Center of Biological Sciences, State University of Londrina, 86057-970, Londrina, Paraná, Brazil., Clemente-Napimoga JT; Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, 13045-755, Campinas, São Paulo, Brazil., Napimoga MH; Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Research Center, 13045-755, Campinas, São Paulo, Brazil., Pitol DL; Department of Morphology, Physiology and Basic Pathology, School of Dentistry, University of São Paulo, 14040-903, Ribeirão Preto, São Paulo, Brazil., Issa JPM; Department of Morphology, Physiology and Basic Pathology, School of Dentistry, University of São Paulo, 14040-903, Ribeirão Preto, São Paulo, Brazil., Fukada SY; Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, 14040-903, Ribeirão Preto, São Paulo, Brazil., Casagrande R; Department of Pharmaceutical Sciences, University Hospital (Health Science Centre), Londrina State University, 86038-350, Londrina, Paraná, Brazil., Verri WA Jr; Department of Pathology, Center of Biological Sciences, State University of Londrina, 86057-970, Londrina, Paraná, Brazil. Electronic address: waverri@uel.br.
Jazyk: angličtina
Zdroj: The Journal of nutritional biochemistry [J Nutr Biochem] 2018 Mar; Vol. 53, pp. 81-95. Date of Electronic Publication: 2017 Nov 05.
DOI: 10.1016/j.jnutbio.2017.10.010
Abstrakt: Titanium dioxide (TiO 2 ) is a common component of orthopedic prosthesis. However, prosthesis wear releases TiO 2 , which induces inflammation and osteolysis in peri-prosthetic tissues. Quercetin is a flavonoid widely present in human diet, which presents biological activities such as antinociceptive, anti-inflammatory and antioxidant effects. Therefore, the effect of intraperitoneal treatment with quercetin in TiO 2 -induced arthritis model was evaluated. In the first set of experiments, mice received injection of TiO 2 (0.1-3 mg/knee joint) and articular mechanical hyperalgesia, edema and histopathology analysis were performed in a 30 days protocol. The dose of 3 mg of TiO 2 showed the most harmful effect, and was chosen to the following experiments. Subsequently, mice received 3 mg of TiO 2 followed by post-treatment with quercetin during 30 days. Quercetin (10-100 mg/kg) inhibited in a dose-dependent manner TiO 2 -induced knee joint mechanical hyperalgesia, edema and leukocyte recruitment and did not induce damage in major organs such as liver, kidney and stomach. The dose of 30 mg/kg was chosen for the subsequent analysis, and reduced histopathological changes such as leukocyte infiltration, vascular proliferation and synovial hyperplasia (pannus formation) on day 30 after TiO 2 challenge. The protective analgesic and anti-inflammatory mechanisms of quercetin included the inhibition of TiO 2 -induced neutrophil and macrophage recruitment, proteoglycan degradation, oxidative stress, cytokine production (TNF-α, IL-1β, IL-6, and IL-10), COX-2 mRNA expression, and bone resorption as well as activation of Nrf2/HO-1 signaling pathway. These results demonstrate the potential therapeutic applicability of the dietary flavonoid quercetin to reduce pain and inflammatory damages associated with prosthesis wear process-induced arthritis.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE