Rheumatoid arthritis and metal compounds—perspectives on the role of oxygen radical detoxification†

Abstract

Rheumatoid arthritis (RA) is characterised by migration of activated phagocytes and other leukocytes into synovial and periarticular tissue. Activated oxygen species and other mediating substances from triggered phagocytes appear to exacerbate and perpetuate the rheumatoid condition. Iron excesses are capable of aggravating the arthritic inflammation, probably through their pro-oxidant potentials. In contrast, therapeutically given gold salts, through a lysosomal loading of the metal, inhibit the triggered cells, thereby reducing the toxic oxygen production. Pharmacological doses of zinc also may immobilise macrophages. Furthermore, the copper-zinc-containing enzyme SOD (superoxide dismutase) can act as a scavenger of toxic oxygen in the tissues. Therapeutic remission of RA has been obtained following intraarticular administration of SOD. Intramuscular administration of copper complexes has induced remission in about 60% of RA patients in open studies. Another drug, penicillamine, that protects cellular membranes against toxic oxygen in vitro, is presumed to act as an antirheumatic via the SOD mimetic activity of its copper complex. Thiomalate and other thiols may possess similar activities. Selenium compounds also may act as oxygen radical scavengers. A significant alleviation of articular pain and morning stiffness was obtained following selenium and vitamin E supplementation in a double-blind study on RA patients. The observations reviewed here indicate that metal compounds and other antioxidants can reduce the rheumatic inflammation by reducing the cellular production and/or concentration of toxic oxygen species.

Dietary manipulation in musculoskeletal conditions

“…At the end of three months, fewer tender or swollen joints, morning stiffness and a reduction in steroid and NSAID use were reported. The third trial using a higher dose (600 µg selenium as selenium-enriched yeast) found no significant effect at four months but a significant improvement at eight months in articular pain index, grip strength and morning stiffness [82]. However, a recent systematic review of trials of antioxidant vitamins and selenium in arthritis has pointed out that the trials are methodologically weak, in particular presenting no between-group statistical comparisons from which proper assessment of the treatment effect can be made [69].…”

“…Early uncontrolled work on copper supplementation in RA reported beneficial effects [82]. A later study by DiSilvestro and colleagues [94] administered 2mg of copper/d for four weeks to 23 RA subjects and 47 matched controls.…”

“…Intra-articular injections of CuZnSOD have been shown to reduce joint inflammation and provide benefit in both RA and OA suggesting the need for adequate intakes of both of these micronutrients [82] [54].…”

Antioxidant Intake and Risks of Rheumatoid Arthritis and Systemic Lupus Erythematosus in Women

“…Both of these diseases are marked by persistent systemic inflammation and tissue damage. Antioxidants are known to protect against tissue damage from reactive oxygen species generated by activated macrophages, monocytes, and granulocytes (1)(2)(3) and to suppress the activity of cytokines, such as tumor necrosis factor-a (4), an important inflammatory mediator in these diseases. In murine models of SLE, supplementation with antioxidants, including b-carotene, a-tocopherol, ascorbic acid, and selenium, reduced autoantibody production and prolonged survival (5)(6)(7).…”

Avaliação da produção de espécies reativas de oxigênio por granulócitos de sangue periférico de pacientes com fibromialgia primária

“…As doenças até então definidas como relacionadas à produção aumentada de ERO apresentam um caráter inflamatório e degenerativo, o que não é observado na fibromialgia. Na reumatologia, uma produção aumentada de ERO tem sido apontada como importante na lesão tecidual observada em processos inflamatórios de doenças como a artrite reumatóide (35) . Na FM, a dor é o sintoma predominante e a participação de radicais livres já foi testada experimentalmente e in vivo em processos de dor.…”