Drug derived radicals: mediators of the side effects of anti-inflammatory drugs?

Reactive oxygen species in rheumatoid arthritis It is now generally accepted that oxygen free radicals and other reactive oxygen species play some part in the pathology of inflammatory joint disease, though whether this is a major or minor part remains to be established.'A radical is any species containing one or more unpaired electrons (denoted by a superscript dot, ).Examples are the superoxide radical (Q2-) and hydroxyl radical (OH,).The term reactive oxygen species is a broader term that includes not only Q°and OH-but also certain non- radical oxygen derived species, such as hydro- gen peroxide (H202) and hypochlorous acid (HOCI), which are potentially, damaging.)Increased formation of reactive oxygen species is probably a generalised response to tissue injury, as may be the increased synthesis of other 'injury mediators' such as prostaglandins, leukotrienes, interleukins, and tumour necrosis factors. 1 2 There is therefore nothing special in showing increased activity of reactive oxygen species in any human disease: it is almost to be expected.1 2 What needs to be done (as for any putatively important injury mediator) is to show that reactive oxygen species are important contributors to disease activity (table 1).This has been exceptionally difficult because reactive oxygen species are hard to measure, but fortunately new methods are becoming avail- able.' Sources of reactive oxygen species in rheumatoid arthritis Synovial fluid neutrophils, and macrophages in the pannus, probably generate some 02and H202 in the inflamed rheumatoid joint.