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Metabolic syndrome and the decreased levels of uric acid by leflunomide favor redox imbalance in patients with rheumatoid arthritis

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Abstract

Oxidative stress plays a role in the pathophysiology of rheumatoid arthritis (RA). The aim of the present study was to verify the influence of metabolic syndrome (MetS) and disease-modifying antirheumatic drugs on nitrosative and oxidative biomarkers in patients with RA. A total of 177 patients with RA and 150 healthy volunteers participated in this study, which measured lipid hydroperoxides, advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), carbonyl protein, total radical-trapping antioxidant parameter (TRAP), uric acid (UA), and C-reactive protein (CRP). NOx and the NOx/TRAP ratio were significantly increased in RA, while no significant differences in lipid hydroperoxides, AOPP, UA, and TRAP levels were found between both groups. Treatment with leflunomide was associated with increased levels of carbonyl protein, and lowered levels in TRAP and UA, while the NOx/TRAP ratio further increased. NOx and the NOx/TRAP ratio were significantly higher in women than in men, while TRAP and UA were significantly lower in women. MetS was accompanied by increased AOPP and UA levels. RA was best predicted by increased NOx/TRAP ratio, CRP, and BMI. In conclusion, our data demonstrated that NOx and NOx/TRAP are strongly associated with RA physiopathology. Our findings suggest that inhibition of iNOS may become an interesting therapeutic approach for the treatment of RA. In addition, the presence of MetS and a decrease in levels of UA by leflunomide favor redox imbalance in RA patients. More studies are needed to evaluate the impact of antioxidant capacity reduction on RA progression.

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Acknowledgements

The study was supported by Grants from Coordination for the Improvement of Higher Level of Education Personnel (CAPES) of Brazilian Ministry of Education; Institutional Program for Scientific Initiation Scholarship (PIBIC) of the National Council for Scientific and Technological Development (CNPq); and State University of Londrina (PROPPG). We thank the University Hospital of State University of Londrina for technical supports.

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Authors and Affiliations

  1. Laboratory of Research in Applied Immunology, University of Londrina, Londrina, Paraná, Brazil

    Neide Tomimura Costa, Bruna Miglioranza Scavuzzi, Daniela Frizon Alfieri & Bruno Alexandre Sekiguchi

  2. Department of Internal Medicine, University of Londrina, Londrina, Paraná, Brazil

    Neide Tomimura Costa & Isaias Dichi

  3. Department of Rheumatology – PUC, Pontifícia Universidade Católica, Londrina, Paraná, Brazil

    Tatiana Mayumi Veiga Iriyoda

  4. Department of Clinical Pathology, Clinical Analysis and Toxicology – University of Londrina, Robert Koch Avenue No. 60 Bairro Cervejaria, Londrina, Paraná, CEP: 86038-440, Brazil

    Marcell Alysson Batisti Lozovoy, Edna Maria Vissoci Reiche & Andréa Name Colado Simão

  5. Post Graduate Program in Clinical and Laboratory Pathophysiology, University of Londrina, Londrina, Paraná, Brazil

    Fabiano Aparecido de Medeiros, Marcelo Cândido de Sá & Pâmela Lonardoni Micheletti

  6. IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, VIC, Australia

    Michael Maes

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Costa, N.T., Scavuzzi, B.M., Iriyoda, T.M.V. et al. Metabolic syndrome and the decreased levels of uric acid by leflunomide favor redox imbalance in patients with rheumatoid arthritis. Clin Exp Med 18, 363–372 (2018). https://doi.org/10.1007/s10238-018-0500-y

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