RESUMO
BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder mainly affecting joints, yet the systemic inflammation can influence other organs and tissues. The objective of this study was to unravel the ameliorative capability of Ondansetron (O) or ß-sitosterol (BS) against inflammatory reactions and oxidative stress that complicates Extra-articular manifestations (EAM) in liver, kidney, lung, and heart of arthritic and arthritic irradiated rats. METHODS: This was accomplished by exposing adjuvant-induced arthritis (AIA) rats to successive weekly fractions of total body γ-irradiation (2 Gray (Gy)/fraction once per week for four weeks, up to a total dose of 8 Gy). Arthritic and/or arthritic irradiated rats were either treated with BS (40 mg/kg b.wt. /day, orally) or O (2 mg/kg) was given ip) or were kept untreated as model groups. RESULTS: Body weight changes, paw circumference, oxidative stress indices, inflammatory response biomarkers, expression of Janus kinase-2 (JAK-2), Signal transducer and activator of transcription 3 (STAT3), high mobility group box1 (HMGB1), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), as well as pro- and anti-inflammatory mediators in the target organs, besides histopathological examination of ankle joints and extra-articular tissues. Treatment of arthritic and/or arthritic irradiated rats with BS or O powerfully alleviated changes in body weight gain, paw swelling, oxidative stress, inflammatory reactions, and histopathological degenerative alterations in articular and non-articular tissues. CONCLUSION: The obtained data imply that BS or O improved the articular and EAM by regulating oxidative and inflammatory indices in arthritic and arthritic irradiated rats.