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   <subfield code="a">Conditional pharmacology: II. Ambivalent effects of aurocyanide, a putative active metabolite of anti-arthritic gold drugs, on human and rat PMN leucocytes</subfield>
   <subfield code="h">[Elektronische Daten]</subfield>
   <subfield code="c">[S. Gadd, M. Whitehouse, B. Vernon-Roberts]</subfield>
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   <subfield code="a">Aurocyanide, and to a lesser extent, aurothiomalate and aurothiosulphate, showed diverse antioxidant/pro-oxidant effects on PMN leucocytes when stimulated ex-vivo to generate hydrogen peroxide. In normal human cells, aurocyanide inhibited peroxide production (ID50 for aurocyanideca. 5 μmol/L) and reduced average cell size more potently than the thiomalate and thiosulphate (ID50 of 200 μmol/L for both). Factors influencing the results included the type of fluorochrome for detecting peroxide and intrinsic variability between human donors. In the presence of azide (1 mmol/L), peroxide production was stimulated but cell size was still reduced. Some PMN stimulants such as fMLP and complement component C5a with aurocyanide only stimulated peroxide production in the presence of azide and had no effect in its absence. In both normal and arthritic rat neutrophils, aurocyanide only stimulated peroxide production but still reduced cell size. These observations show that mechanisms of action of these gold drugs may be related to the effects of aurocyanide but there are differences between rat and human cells in vitro. A single dose of aurocyanide (10 mg/kg) co-administered with two arthritogenic adjuvants effectively prevented arthritis development in rats. Much higher doses, bordering on toxic, were required for two gold-thiolates to exhibit similar activity.</subfield>
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