Abstract
The effect of D-penicillamine (D-P) on proliferation of human endothelial cells (ECs) and synovial fibroblastic cells (SFCs) was examined. D-P inhibited DNA synthesis of both ECs and SFCs in the presence of copper sulfate. Inhibition of DNA synthesis occurred in a dose-dependent fashion and a significant inhibition was attained at 60 μM D-P, a level which is attained in the serum of treated patients. Similar inhibition was observed by other thiols but not by disulfides. D-P, in vitro, produced hydrogen peroxide in the presence of copper sulfate. As the inhibition observed by D-P and copper sulfate was reversed almost to the control level by simultaneous addition of catalase and horseradish peroxide, it is suggested that inhibition of EC and SFC DNA synthesis is due to the action of hydrogen peroxide produced by D-P and cupric ion.D-P, therefore, may suppress the growth of pannus and synovial fibrosis by inhibition of synovial vessel growth and SFC proliferation and in this way, may reduce rheumatoid inflammation.
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