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d-Penicillamine metabolism in anin-vivo model of inflamed synovium

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Abstract

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.

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Authors and Affiliations

  1. Department of Pharmacology, University of Western Australia, 6009, Nedlands, Western Australia

    D. A. Joyce

  2. Sutton Rheumatism Research Laboratory, University of Sydney, at the Royal North Shore Hospital, 2065, St Leonards, N.S.W., Australia

    M. J. Forrest & P. M. Brooks

Authors
  1. D. A. Joyce
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  2. M. J. Forrest
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  3. P. M. Brooks
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Joyce, D.A., Forrest, M.J. & Brooks, P.M. d-Penicillamine metabolism in anin-vivo model of inflamed synovium. Agents and Actions 25, 336–343 (1988). https://doi.org/10.1007/BF01965040

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