Rheumatoid joint antioxidants

This chapter addresses (1) the mechanisms, antioxidant defences and consequences in relation to free-radical production in the inflamed rheumatoid joint (2) lipid abnormalities in RA (3) the potential contribution of ox-LDL to RA (the role of ox-LDL in coronary heart disease is discussed in Chapters 2 and 3 and will not be fully discussed here) and (4) the therapeutic aspects of chain-breaking antioxidant interventions in RA. 

Mechanisms, Antioxidant Defences and Consequences of Free-radical Production in the Rheumatoid Joint... 

Esterbauer et al. (1991) have demonstrated that /3-carotene becomes an effective antioxidant after the depletion of vitamin E. Our studies of LDL isolated from matched rheumatoid serum and synovial fluid demonstrate a depletion of /8-carotene (Section 2.2.2.2). Oncley et al. (1952) stated that the progressive changes in the absorption spectra of LDL were correlated with the autooxidation of constituent fatty acids, the auto-oxidation being the most likely cause of carotenoid degradation. The observation that /3-carotene levels in synovial fluid LDL are lower than those of matched plasma LDL (Section 2.2.2) is interesting in that /3-carotene functions as the most effective antioxidant under conditions of low fOi (Burton and Traber, 1990). As discussed above (Section 2.1.3), the rheumatoid joint is both hypoxic and acidotic. We have also found that the concentration of vitamin E is markedly diminished in synovial fluid from inflamed joints when compared to matched plasma samples (Fairburn etal., 1992). This difference could not be accounted for by the lower concentrations of lipids and lipoproteins within synovial fluid. The low levels of both vitamin E and /3-carotene in rheumatoid synovial fluid are consistent with the consumption of lipid-soluble antioxidants within the arthritic joint due to their role in terminating the process of lipid peroxidation (Fairburn et al., 1992). 

Fig. 2.8. Factors controlling the production of free radicals in cells and tissues (Rice-Gvans, 1990a). Free radicals may be generated in cells and tissues through increased radical input mediated by the disruption of internal processes or by external influences, or as a consequence of decreased protective capacity. Increased radical input may arise through excessive leukocyte activation, disrupted mitochondrial electron transport or altered arachidonic acid metabolism. Delocalization or redistribution of transition metal ion complexes may also induce oxidative stress, for example, microbleeding in the brain, in the eye, in the rheumatoid joint. In addition, reduced activities or levels of protectant enzymes, destruction or suppressed production of nucleotide coenzymes, reduced levels of antioxidants, abnormal glutathione metabolism, or leakage of antioxidants through damaged membranes, can all contribute to oxidative stress.

Halliwell, B., Wasil, M., and Grootveld, M., 1987, Biologically significant scavenging of the myeloperoxidase-derived oxidant hypochlorous acid by ascorbic acid Implications for antioxidant protection in the inflamed rheumatoid joint, FEBS Lett. 213 15-18. 

Tea extracts have been demonstrated to inhibit a wide range of inflammatory responses and may be useful in treating chronic inflammatory states. For example, rheumatoid arthritis is an inflammatory disease that causes pain, swelling, stiffness and loss of function in the joints. The antioxidants in green tea may prevent or reduce the severity of these symptoms by reducing inflammation and slowing cartilage breakdown (Adcocks et al, 2002 Haqqi et al, 1999). 

The influence of antioxidants (e.g. vitamin E or a-tocopherol, vitamin C or ascorbic acid, and carotenoids, including P-carotene and lycopene) on autoimmune diseases has not been extensively studied. There is some evidence that damage induced by reactive oxygen species contributes to the destruction of pancreatic beta cells, brain tissue, and joints seen in diabetes mellitus type 1, multiple sclerosis, and rheumatoid arthritis, respectively. However, there are few prospective studies of antioxidant intake and risk of autoimmune diseases. Although there is some evidence of a reduced risk of rheumatoid arthritis and lupus with higher intake or serum levels of antioxidants, there are inconsistent findings with respect to which antioxidants or foods are involved (Comstock et al., 1997 Knekt et al., 2000 Cerhan et al., 2003). Only one prospective study of antioxidants and risk of multiple sclerosis is available, and that study reported no association with intakes of vitamin C, vitamin E, or carotenoids (Zhang et al., 2001). 

Oxidation stress is unbalanced between prooxidants and natural antioxidants in body that lead to several diseases such as rheumatoid. Hyaluronic acid (HA), is a high molecular weight biopolysacharide, is found in the extracellular matrix of soft connective tissues and is particularly concentrated in synovial fluid (SF). Half-live time of Hyaluronan in SF is approximately 12 hrs in normal conditions. This process is accelerated under normal oxidation stress that generates troubles in human joints. 

---