The flavonoid quercetin inhibits titanium dioxide (TiO2)-induced chronic arthritis in mice

Author(s):Show less -

Borghi, Sergio M. ^[1] ; Mizokami, Sandra S. ^[1] ; Pinho-Ribeiro, Felipe A. ^[1] ; Fattori, Victor ^[1] ; Crespigio, Jefferson ^[1] ; Clemente-Napimoga, Juliana T. ^[2] ; Napimoga, Marcelo H. ^[2] ; Pitol, Dimitrius L. ^[3] ; Issa, Joao P. M. ^[3] ; Fukada, Sandra Y. ^[4] ; Casagrande, Rubia ^[5] ; Verri, Jr., Waldiceu A. ^[1]

Affiliation

^[1] Univ Estadual Londrina, Ctr Biol Sci, Dept Pathol, BR-86057970 Londrina, Parana - Brazil

^[2] Sao Leopoldo Mandic Inst & Res Ctr, Lab Immunol & Mol Biol, BR-13045755 Campinas, SP - Brazil

^[3] Univ Sao Paulo, Sch Dent, Dept Morphol Physiol & Basic Pathol, BR-14040903 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, BR-14040903 Ribeirao Preto, SP - Brazil

^[5] Univ Estadual Londrina, Hlth Sci Ctr, Univ Hosp, Dept Pharmaceut Sci, BR-86038350 Londrina, Parana - Brazil

• Document type: Journal article
• Source: JOURNAL OF NUTRITIONAL BIOCHEMISTRY; v. 53, p. 81-95, MAR 2018.
• Web of Science Citations: 13

Abstract

Titanium dioxide (TiO2) is a common component of orthopedic prosthesis. However, prosthesis wear releases TiO2, 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 TiO2-induced arthritis model was evaluated. In the first set of experiments, mice received injection of TiO2 (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 TiO2 showed the most harmful effect, and was chosen to the following experiments. Subsequently, mice received 3 mg of TiO2 followed by post-treatment with quercetin during 30 days. Quercetin (10-100 mg/kg) inhibited in a dose-dependent manner TiO2-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 TiO2 challenge. The protective analgesic and anti-inflammatory mechanisms of quercetin included the inhibition of TiO2-induced neutrophil and macrophage recruitment, proteoglycan degradation, oxidative stress, cytokine production (TNF-alpha, IL-1 beta, 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. (C) 2017 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 15/09034-0 - The role of O-glycosylation on the modulation of osteoclastogenesis and bone resorption
• Grantee: Sandra Yasuyo Fukada Alves
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/15014-9 - Evaluation of the effect of 15d-PGJ2-loaded on polymeric biodegradable nanoparticles to control the evolution of the experimental periodontal disease
• Grantee: Marcelo Henrique Napimoga
• Support Opportunities: Regular Research Grants