1. Activation of the Nrf2/HO-1 signaling pathway by dimethyl fumarate ameliorates complete Freund's adjuvant-induced arthritis in rats
- Author
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Ravinder Naik Dharavath, Kanwaljit Chopra, Jatinder Dhaliwal, Roshan Lal, and Navneet Dhaliwal
- Subjects
Pain Threshold ,0301 basic medicine ,NF-E2-Related Factor 2 ,Dimethyl Fumarate ,Freund's Adjuvant ,Anti-Inflammatory Agents ,Arthritis ,Pharmacology ,medicine.disease_cause ,Antioxidants ,Superoxide dismutase ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Animals ,Rats, Wistar ,chemistry.chemical_classification ,Analgesics ,Dimethyl fumarate ,biology ,Glutathione peroxidase ,Glutathione ,medicine.disease ,Malondialdehyde ,Arthritis, Experimental ,Oxidative Stress ,030104 developmental biology ,chemistry ,Antirheumatic Agents ,Myeloperoxidase ,Heme Oxygenase (Decyclizing) ,biology.protein ,Cytokines ,Female ,Joints ,Inflammation Mediators ,030217 neurology & neurosurgery ,Oxidative stress ,Signal Transduction - Abstract
The nuclear factor erythroid 2-related factor (Nrf2) signaling pathway has recently emerged as a novel therapeutic target in treating various diseases. Therefore, the present study aimed to assess the protective role of the Nrf2 activator, dimethyl fumarate (DMF) in the complete Freund's adjuvant (CFA)- induced arthritis model. DMF (25, 50, and 100 mg/kg) and dexamethasone (2 mg/kg) were orally administered for 14 days. Pain-related tests, paw volume, and arthritic scores were measured weekly. Serum TNF-α, IL-1β, cyclic citrullinated peptide (CCP), C-reactive protein (CRP), and rheumatoid factor (RF) levels were estimated. Nitrite, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), catalase (CAT), and myeloperoxidase (MPO) levels were also evaluated. NF-κB, Nrf2, HO-1, and COX-2 levels were estimated in the joint tissue. DMF treatment exerted anti-arthritic activity by enhancing the nociceptive threshold, improving arthritis scores, and reducing paw edema. Also, DMF suppressed changes in oxidative stress markers and inflammatory mediators and enhanced Nrf2 and HO-1 levels in CFA-injected rats. These findings indicate that the anti-arthritic activity of DMF may be mediated by the activation of the Nrf2/HO-1 pathway, which reduced oxidative damage and inflammation.
- Published
- 2021