Background Studies about cytotoxicity and genotoxicity in rheumatoid arthritis (RA) are limited and the toxicity of Disease Modifying Anti-Rheumatic Drugs (DMARDs) commonly used in treatment is still a concern.
Objectives to assess cytotoxicity and genotoxicity in RA and the possible cyto and genotoxic effects of some DMARDs used in treatment.
Methods The study included 30 female RA patients divided according to treatment into three groups and ten healthy controls. Two groups received DMARDs for at least 3 months period: methotrexate (MTX) only group (n=12 patients), MTX with SSZ (sulphasalazine) group (n=8) and ten DMARDs naieve RA who received only Non Steroidal Anti-Inflammatory Drugs (NSAIDs). The MTX dose was 15–20 mg/wk, SSZ dose was 1.5–2 gm daily. All RA on DMARDs received concomitant daily folic acid dose of 0.5 mg.Peripheral blood samples were taken to assess the cytotoxicity by chromosomal analysis (karyotyping) using solid Giemsa stain and GTG-banding according to the International System for Human Chromosome Nomenclature. Genotoxicity and DNA damage was assessed by the miconucleustest usin g cytochalasin –B.
Results Compared to controls, RA patients had significantly higher chromosomal aberrations (CAs) in the form of breaks, satellite association, endoreduplication, aneuploidy, double minute, and other aberrations. There was also a statistically significant increase in the markers of genotoxicity in RA patients compared to controls: micronuclei (MN), nucleoplasmic bridges (NPB) and necrotic and/or apoptotic cells (Table1). CAs were found in all RA groups, those receiving DMARDs as well as the DMARD naieve group. CAs were significantly higher in MTX and in MTX-SSZ group when compared to RA on NSAIDs only. Meanwhile, there was no significant difference between the CAs in the MTX and the MTX-SSZ groups. In addition, the number of binucleated (BN) cells with MN, NPB, and the necrotic and/or apoptotic cells was statistically higher in MTX-RA and MTX-SSZ-RA compared to the NSAIDs group. Whereas, no statistical difference was found between the two DMARDs groups.RA patients who were on DMARDs for a longer duration (>5 years) showed a statistically significant increase in all cytotoxicity and genotoxicity markers than those for shorter duration (<5 years).
Conclusions RA patients show significantly increased markers of cytotoxicity and genotoxicity, regardless the type of medications received, sugggesting them to represent underestimated disease features which could provide new insights into its pathogenesis. MTX further aggrevates the cyto- and genotoxicity, whereas SSZ combination does not seem to play additional role and concomitant folic acid supplementation does not provide the sufficient protection.
Disclosure of Interest None declared
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