Influence of disease-modifying antirheumatic drugs on oxidative and nitrosative stress in patients with rheumatoid arthritis

Inflammopharmacology. 2018 Oct;26(5):1151-1164. doi: 10.1007/s10787-018-0514-9. Epub 2018 Jul 30.

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.

Keywords: Disease-modifying antirheumatic drugs; Nitrosative stress; Oxidative stress; Rheumatoid arthritis.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / metabolism
  • Etanercept / therapeutic use
  • Humans
  • Infliximab / therapeutic use
  • Leflunomide / therapeutic use
  • Methotrexate / therapeutic use
  • Nitrosative Stress / drug effects*
  • Oxidative Stress / drug effects*

Substances

  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Infliximab
  • Leflunomide
  • tocilizumab
  • Etanercept
  • Methotrexate