THE LEVEL OF NITRIC OXIDE METABOLITES AND NOS2 GENE TRANSCRIPTS IN RHEUMATOID ARTHRITIS

DOI: https://doi.org/10.29296/24999490-2018-04-03

L.V. Topchieva(1), O.V. Balan(1), I.E. Malysheva(1), O.Yu. Barysheva(2), I.M. Marusenko(2), O.A. Vaskova(2) 1-Institute of Biology of Karelian Research Centre Russian Academy of Sciences, Russian Federation, Pushkinskaya str., 11, Petrozavodsk, Russian Federation, 185910; 2-Petrozavodsk State University, Lenina pr., 33, Petrozavodsk, Russian Federation, 185910 E-mail: [email protected]

The aim of this work was to study the effect of methotrexate, glucocorticoids and nonsteroidal anti-inflammatory drugs on the plasma levels of nitric oxide metabolites, as well as the level of NOS2 gene transcripts in peripheral blood leukocytes (PBL) in rheumatoid arthritis (RA) patients. Material and methods. Samples of venous blood from healthy donors and RA patients both at the onset of the disease (before therapy) and from cases treated with methotrexate, prednisolone and diclofenac (nonsteroidal anti-inflammatory drug) individually as well as in various combinations were used. The total plasma level of nitrites and nitrates was measured by calorimetric method using the Griss reagent. The expression of NOS2 gene was study by real-time PCR. Results. The nitric oxide plasma level in RA patients was shown to be much higher if compared to healthy people. The therapy with anti-inflammatory drugs promoted a decrease of plasma nitric oxide concentration. The best effect on the NO reduction was demonstrated by the combination treatment with methotrexate-prednisolone. The mRNA NOS2 gene expression in peripheral blood leukocytes in RA patients at the onset of the disease was significantly higher when compared to healthy people and patients with anti-inflammatory therapy. Conclusion. The increased level of NOS2 gene transcripts in peripheral blood leukocytes in RA patients at the onset of the disease indicates to the involvement of NOS2 in the hyperproduction of nitric oxide and the pathogenesis of this disease. Anti-inflammatory therapy promotes the reduction of the plasma level of NO metabolites, apparently due to inhibition of the transcription activity of the NOS2 gene. The effectiveness of this process depends on the pharmacological properties of used drugs.
Keywords: 
rheumatoid arthritis, nitric oxide metabolites, inducible nitric oxide synthase, NOS2 gene expression, anti-inflammatory drugs
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