d-Penicillamine metabolism in anin-vivo model of inflamed synovium
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Oxidation to disulphides is the chief metabolic transformation ofd-penicillamine (d-pen) in patients with rheumatoid arthritis. Oxidation also occurs in many biological fluidsin-vitro. Reduction of oxygen species may accompany the oxidation ofd-pen under appropriate conditions and may mediate the anti-rheumatic action ofd-pen. The transformation ofd-pen therefore was examined in anin-vivo model of inflamed synovium.
Subcutaneous air-pouches of groups of rats were treated with saline, 10% serum or 10% zymosan activated serum (ZAS). The transformation ofd-pen to low molecular weight (LMW) metabolites and protein conjugates within the pouch was then assessed. The concentrations of total protein were significantly higher in the serum and ZAS-treated groups than in the saline-treated group and the inflammatory cell counts were significantly higher in the ZAS-treated group than in either of the other groups, as expected.d-pen oxidised rapidly to LMW metabolites and smaller amounts ofd-pen-protein conjugate (d-pen-protein) in the air pouches of all animals. The rates of oxidation to LMW metabolites were greater in the ZAS-treated animals than the saline-treated group (p<0.005). The concentrations ofd-pen-protein conjugate were also greater for the serum-treated and ZAS-treated animals than for the saline controls (p<0.005 in each case) at all times.
Oxidation ofd-pen therefore occurs at this site of inflammation and is influenced by local conditions. This may be important to understanding the forms in whichd-pen exists in inflamed synovial joints and the way it may exert its antirheumatic activity.
KeywordsRheumatoid Arthritis Arthritis Inflammatory Cell Local Condition Disulphide
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