Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease associated with oxidative stress that causes excruciating
pain, discomfort, and joint destruction.
Ebselen (EB), a synthesized versatile organo-
selenium compound, protects cells from
reactive oxygen species (ROS)-induced injury by mimicking
glutathione peroxidase (GPx) action. This study aimed to investigate the
antioxidant and anti-inflammatory effects of EB in an arthritic irradiated model. This goal was achieved by subjecting adjuvant-induced
arthritis (AIA) rats to fractionated whole body γ-irradiation (2 Gy/fraction once per week for 3 consecutive weeks, for a total dose of 6 Gy) and treating them with EB (20 mg/kg/day, p.o) or
methotrexate (MTX; 0.05 mg/kg; twice/week, i.p) as a reference anti-RA
drug. The arthritic clinical signs, oxidative stress and
antioxidant biomarkers, inflammatory response, expression of
NOD-like receptor protein-3 (NLRP-3)
inflammasome, receptor activator of nuclear factor κB
ligand (RANKL), nuclear factor-κB (NF-κB), apoptotic indicators (
caspase 1 and
caspase 3), cartilage integrity marker (
collagen-II), and histopathological examination of ankle joints were assessed. EB notably improved the severity of arthritic clinical signs, alleviated joint histopathological lesions, modulated oxidative stress and
inflammation in serum and synovium, as well as reduced NLRP-3, RANKL, and caspase3 expression while boosting
collagen-II expression in the ankle joints of arthritic and arthritic irradiated rats with comparable potency to MTX. Our findings suggest that EB, through its
antioxidant and anti-inflammatory properties, has anti-arthritic and radioprotective properties in an arthritic irradiated model.