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Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents


ISSN (Print): 1568-0134
ISSN (Online): 1568-0134

Oxidative Stress and the Use of Antioxidants for the Treatment of Rheumatoid Arthritis

Author(s): Charles Kunsch, James A. Sikorski and Cynthia L. Sundell

Volume 5, Issue 3, 2005

Page: [249 - 258] Pages: 10

DOI: 10.2174/1568013054022490

Price: $65


Oxidant stress as a result of increased production of reactive oxygen species (ROS) or a reduction in the bodys endogenous antioxidant defense system is a hallmark of chronic inflammatory diseases including rheumatoid arthritis (RA). A primary source of ROS in RA is leukocytes (i.e. activated macrophages, neutrophils, mast cells and lymphocytes) that are recruited to, and that accumulate within, the synovium. ROS and reactive nitrogen species (RNS) can contribute to the pathogenesis of RA in a variety of ways including: induction of membrane oxidation and instability, irreversible damage to proteins and DNA, cartilage damage and induction of bone resorption. In addition, it has recently been appreciated that ROS/RNS can also modulate a variety of signaling events that control gene expression and effect cellular processes that participate in chronic inflammation. These include effects on vascular tone, cell growth and proliferation and induction of pro-inflammatory genes. Consistent with a role for oxidant stress in the pathogenesis of RA, a number of preclinical and clinical studies have correlated increases in markers of oxidative stress and lower levels of the bodys natural antioxidants with disease severity. Accordingly, a variety of methods aimed at reducing ROS production, scavenging ROS or restoring the antioxidant balance have been tested with some success in experimental models of RA and in clinical trials. Although considerable data supports the notion that antioxidant-based drugs could prove beneficial in the treatment of RA, very few have been evaluated clinically and to date none have demonstrated clinical proof-ofconcept in Phase II clinical studies.

Keywords: antioxidants, rheumatoid arthritis, oxidant stress, reactive oxygen species

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