Neide Tomimura Costa1, Tatiana Mayumi Veiga Iriyoda2, Daniela Frizon Alfieri3, Andréa Name Colado Simão3,4, Isaias Dichi5. 1. Department of Rheumatology, University of Londrina, Londrina, Paraná, Brazil. 2. Department of Rheumatology, Pontifícia Universidade Católica (PUC), Londrina, Paraná, Brazil. 3. Research Laboratory of Applied Immunology, University of Londrina, Londrina, Paraná, Brazil. 4. Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Londrina, Paraná, Brazil. 5. Department of Internal Medicine, University of Londrina, Robert Koch Avenue no. 60 Bairro Cervejaria, Londrina, Paraná, CEP: 86038-440, Brazil. dichi@sercomtel.com.br.
Abstract
BACKGROUND: Nitro-oxidative stress plays a central role in the pathogenesis of rheumatoid arthritis (RA) and several articles show correlation with disease activity. However, the influence and mechanisms by which disease-modifying antirheumatic drugs (DMARDs) may interfere with nitro-oxidative stress are poorly understood. OBJECTIVE: To show the available data on the effect of the DMARDs on the nitro-oxidative stress in RA patients. METHODS: A bibliographic search was carried out in the electronic databases PUBMED, Lilacs, Scientific Electronic Library Online (SCIELO), and Science Direct and the research was limited to human studies, independently of the publication date. RESULTS: Most studies were performed with infliximab (IFX, 4 articles), tocilizumab (TCZ, 3 articles) and methotrexate (MTX, 2 articles). MTX and leflunomide showed similar results with reduction of nitric oxide. The studies with TCZ verified a marked decrease of reactive oxygen and nitrogen species. Most studies with IFX found a reduction of protein oxidation, evaluated by protein carbonyl measurement. In the present review, the most remarkable results were observed with the increase of the antioxidant defenses through several markers and antioxidant systems. The only study with etanercept showed very similar results to those obtained with MTX, with decreased pentosidine and oxidative DNA damage. CONCLUSIONS: The majority of the studies reported in this work showed an improvement in the redox state, which could be related to success of the therapy. Thus, oxidative and nitrosative stress markers may be useful to early evaluate the response of DMARDs in patients with RA.
BACKGROUND:Nitro-oxidative stress plays a central role in the pathogenesis of rheumatoid arthritis (RA) and several articles show correlation with disease activity. However, the influence and mechanisms by which disease-modifying antirheumatic drugs (DMARDs) may interfere with nitro-oxidative stress are poorly understood. OBJECTIVE: To show the available data on the effect of the DMARDs on the nitro-oxidative stress in RApatients. METHODS: A bibliographic search was carried out in the electronic databases PUBMED, Lilacs, Scientific Electronic Library Online (SCIELO), and Science Direct and the research was limited to human studies, independently of the publication date. RESULTS: Most studies were performed with infliximab (IFX, 4 articles), tocilizumab (TCZ, 3 articles) and methotrexate (MTX, 2 articles). MTX and leflunomide showed similar results with reduction of nitric oxide. The studies with TCZ verified a marked decrease of reactive oxygen and nitrogen species. Most studies with IFX found a reduction of protein oxidation, evaluated by protein carbonyl measurement. In the present review, the most remarkable results were observed with the increase of the antioxidant defenses through several markers and antioxidant systems. The only study with etanercept showed very similar results to those obtained with MTX, with decreased pentosidine and oxidative DNA damage. CONCLUSIONS: The majority of the studies reported in this work showed an improvement in the redox state, which could be related to success of the therapy. Thus, oxidative and nitrosative stress markers may be useful to early evaluate the response of DMARDs in patients with RA.
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