Hesperidin Methyl Chalcone Reduces the Arthritis Caused by TiO 2 in Mice: Targeting Inflammation, Oxidative Stress, Cytokine Production, and Nociceptor Sensory Neuron Activation

• Published in: Molecules (Basel, Switzerland) Switzerland), 2023-01, Vol.28 (2)
• Main Authors: Artero, Nayara A, Manchope, Marília F, Carvalho, Thacyana T, Saraiva-Santos, Telma, Bertozzi, Mariana M, Carneiro, Jessica A, Franciosi, Anelise, Dionisio, Amanda M, Zaninelli, Tiago H, Fattori, Victor, Ferraz, Camila R, Piva, Maiara, Mizokami, Sandra S, Camilios-Neto, Doumit, Casagrande, Rubia, Verri, Waldiceu A
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Antioxidants - pharmacology; Arthritis - drug therapy; Chalcones - therapeutic use; Cytokines - metabolism; Hesperidin; Hyperalgesia - drug therapy; Inflammation - drug therapy; Inflammation - metabolism; Mice; Nociceptors - metabolism; Oxidative Stress
• ISSN: 1420-3049

Arthroplasty is an orthopedic surgical procedure that replaces a dysfunctional joint by an orthopedic prosthesis, thereby restoring joint function. Upon the use of the joint prosthesis, a wearing process begins, which releases components such as titanium dioxide (TiO ) that trigger an immune response in the periprosthetic tissue, leading to arthritis, arthroplasty failure, and the need for revision. Flavonoids belong to a class of natural polyphenolic compounds that possess antioxidant and anti-inflammatory activities. Hesperidin methyl chalcone's (HMC) analgesic, anti-inflammatory, and antioxidant effects have been investigated in some models, but its activity against the arthritis caused by prosthesis-wearing molecules, such as TiO , has not been investigated. Mice were treated with HMC (100 mg/kg, intraperitoneally (i.p.)) 24 h after intra-articular injection of 3 mg/joint of TiO , which was used to induce chronic arthritis. HMC inhibited mechanical hyperalgesia, thermal hyperalgesia, joint edema, leukocyte recruitment, and oxidative stress in the knee joint (alterations in gp91 , GSH, superoxide anion, and lipid peroxidation) and in recruited leukocytes (total reactive oxygen species and GSH); reduced patellar proteoglycan degradation; and decreased pro-inflammatory cytokine production. HMC also reduced the activation of nociceptor-sensory TRPV1 and TRPA1 neurons. These effects occurred without renal, hepatic, or gastric damage. Thus, HMC reduces arthritis triggered by TiO , a component released upon wearing of prosthesis.