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Clinical and Experimental Medicine

, Volume 18, Issue 3, pp 363–372 | Cite as

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

  • Neide Tomimura Costa
  • Bruna Miglioranza Scavuzzi
  • Tatiana Mayumi Veiga Iriyoda
  • Marcell Alysson Batisti Lozovoy
  • Daniela Frizon Alfieri
  • Fabiano Aparecido de Medeiros
  • Marcelo Cândido de Sá
  • Pâmela Lonardoni Micheletti
  • Bruno Alexandre Sekiguchi
  • Edna Maria Vissoci Reiche
  • Michael Maes
  • Andréa Name Colado Simão
  • Isaias Dichi
Original Article

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.

Keywords

Rheumatoid arthritis Oxidative stress Nitrosative stress Metabolic syndrome Leflunomide 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

All the participants included in this study provided written informed consent.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Neide Tomimura Costa
    • 1
    • 2
  • Bruna Miglioranza Scavuzzi
    • 1
  • Tatiana Mayumi Veiga Iriyoda
    • 3
  • Marcell Alysson Batisti Lozovoy
    • 4
  • Daniela Frizon Alfieri
    • 1
  • Fabiano Aparecido de Medeiros
    • 5
  • Marcelo Cândido de Sá
    • 5
  • Pâmela Lonardoni Micheletti
    • 5
  • Bruno Alexandre Sekiguchi
    • 1
  • Edna Maria Vissoci Reiche
    • 4
  • Michael Maes
    • 6
  • Andréa Name Colado Simão
    • 4
  • Isaias Dichi
    • 2
  1. 1.Laboratory of Research in Applied ImmunologyUniversity of LondrinaLondrinaBrazil
  2. 2.Department of Internal MedicineUniversity of LondrinaLondrinaBrazil
  3. 3.Department of Rheumatology – PUCPontifícia Universidade CatólicaLondrinaBrazil
  4. 4.Department of Clinical PathologyClinical Analysis and Toxicology – University of LondrinaLondrinaBrazil
  5. 5.Post Graduate Program in Clinical and Laboratory PathophysiologyUniversity of LondrinaLondrinaBrazil
  6. 6.IMPACT Strategic Research Centre, School of MedicineDeakin UniversityGeelongAustralia

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