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Background: Rheumatoid arthritis (RA) is an autoimmune disorder that deteriorates joints and can affect various physiological systems if not properly managed. The persistent joint inflammation and oxidative damage caused by RA can lead to genomic instability, a primary feature of most cancer cells. In RA, the prevalence of malignancy is comparatively higher than in the general population. However, it is unclear if the disease itself or its treatments induce susceptibility to neoplastic disorders. Our goal was to study genomic instability in the arthritic mouse model, namely DNA damage and repair and determine if the long-term use of the biological agent rituximab can impact these changes.
Results: Our results show that rituximab did not disrupt genomic stability at the tested regimen. Arthritic mice had more spontaneous DNA damage and a slower repair rate than control mice. Redox imbalance, oxidative DNA damage, and disturbance in the DNA repair pathways are also increased in arthritic mice. Meanwhile, rituximab treatment reduced oxidative DNA damage and accelerated DNA repair rate, improving redox balance and restoring the disturbances in the DNA repair gene expression at both mRNA as determined by RT2 Profiler PCR array and protein levels as determined by Western blotting analysis in arthritic animals. Additionally, the ameliorative effect of rituximab has also been shown by its ability to reduce the severity of joint inflammation and histopathological alterations induced by arthritis.
Conclusions: The findings indicate that rituximab is a non-genotoxic, safe, effective drug for the treatment of RA and its complications.
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