The activation of gold complexes by cyanide produced by polymorphonuclear leukocytes--I. The effects of aurocyanide on the oxidative burst of polymorphonuclear leukocytes.
It has been suggested that the antiarthritic gold complex, aurothiomalate (Autm), is activated by its conversion to aurocyanide by polymorphonuclear leukocytes (PMN) which generate cyanide from thiocyanate. In an examination of this hypothesis, a study has been conducted on the effects of aurocyanide on the oxidative burst of polymorphonuclear leukocytes (PMN) and monocytes activated by phorbol myristate acetate (PMA). Aurocyanide produced delayed inhibition of the oxidative burst as shown by its effect on both lucigenin and luminol-dependent chemiluminescence and on the production of superoxide. It was a more potent inhibitor of luminol-dependent chemiluminescence than free thiomalate and other by-products of the reaction between Autm and cyanide. Aurocyanide had a biphasic effect on the PMA-stimulated hexose monophosphate shunt of PMN, with enhancement at 0.1 microM and inhibition at 10 and 100 microM. The activity of aurocyanide was also compared with that of auranofin, an orally active gold complex, which inhibits a variety of functions of PMN and monocytes. At low concentrations, auranofin produced delayed inhibition of chemiluminescence in a similar fashion to aurocyanide but at high concentrations was an immediate inhibitor of the oxidative burst.
Rudkowski
R
R
Prince of Wales Childrens' Hospital, University of N.S.W., Sydney, Australia.
Graham
G G
GG
Champion
G D
GD
Ziegler
J B
JB
D001310:Auranofin / Q000494:pharmacology; D002470:Cell Survival; D003485:Cyanates; D003486:Cyanides / Q000494:pharmacology*; D003574:Cytochrome c Group / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D006046:Gold / Q000494:pharmacology*; D017612:Gold Compounds; D006801:Humans; D007700:Kinetics; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003485:Cyanates; D003486:Cyanides; D003574:Cytochrome c Group; D017612:Gold Compounds; C043041:gold cyanide; D001310:Auranofin; D006046:Gold; D003847:Deoxyglucose; D013755:Tetradecanoylphorbol Acetate