The activation of gold complexes by cyanide produced by polymorphonuclear leukocytes--II. Evidence for the formation and biological activity of aurocyanide.
Experiments have been conducted to investigate a possible mechanism which might explain why aurothiomalate (Autm), a gold complex used in the treatment of rheumatoid arthritis, is active in vivo but not in vitro, by testing the hypothesis that Autm is converted to aurocyanide by activated polymorphonuclear leukocytes (PMN) which generate cyanide from thiocyanate, an anion which is present in plasma at concentrations ranging from 20 to 200 microM. Two-stage experiments were conducted in which PMN, in the first stage, were activated by opsonized zymosan in the presence of Autm both with and without thiocyanate. Then, in the second stage, the effect of the drugs on superoxide (O2-) production stimulated by a further addition of zymosan was measured. Autm at concentrations of 10 and 100 microM decreased O2- production if thiocyanate was present, but not if it was absent. By contrast, preformed aurocyanide at 10 and 100 microM decreases O2- production by PMN stimulated by opsonized zymosan both in the presence and absence of thiocyanate. Changes in the ultraviolet spectra of the supernatants of PMN indicated that aurocyanide was formed by activated PMN in the presence of thiocyanate but not in its absence.
Graham
G G
GG
Department of Pharmacology, University College London, U.K.
Dale
M M
MM
D003485:Cyanates; D003486:Cyanides / Q000378:metabolism* / Q000494:pharmacology; D006046:Gold / Q000378:metabolism* / Q000494:pharmacology; D017612:Gold Compounds; D006052:Gold Sodium Thiomalate / Q000494:pharmacology; D006801:Humans; D009504:Neutrophils / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013481:Superoxides / Q000378:metabolism; D013870:Thiomalates / Q000494:pharmacology
D003485:Cyanates; D003486:Cyanides; D017612:Gold Compounds; D013870:Thiomalates; C043041:gold cyanide; D013481:Superoxides; D006052:Gold Sodium Thiomalate; D006046:Gold