Effects of gold-chloroquine complexes on respiratory burst of polymorphonuclear leukocytes.
The effects of gold-chloroquine derivatives with the formula [Au(PR3)(CQ)]PF6 (where R = Ph (1), Et or Me) on the superoxide anion production by human neutrophils (PMNs, polymorphonuclear cells) were investigated. When these complexes (0.1-3 mumol/l) were added to PMNs prior to the activators formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA), they inhibited isoluminol-horseradish peroxidase-dependent chemiluminescence (CLisol). The inhibition was a direct result of effects on PMNs since chemiluminescence in the cell-free system (horseradish peroxidase-hydrogen peroxidase-isoluminol) was not affected. The above mentioned concentrations of the complexes did not show in vitro toxicity on the cells. On the other hand, when 1 mumol/l of complex 1 was added to cells after stimulation, the chemiluminescence of PMNs stimulated by PMA was inhibited, but not the chemiluminescence stimulated by fMLP. The gold-chloroquine binding was essential for the referred activity as chemiluminescence was not influenced by the precursors chloroquine (CAS 54-05-7) and AuCl(PPh3). Furthermore, the extent of inhibition of chemiluminescence in PMNs activated by PMA did not increase with the duration of preincubation in presence of 1 mumol/l of 1. Extensive washing of cells after preincubation with 1 mumol/l of 1 reversed the aforementioned inhibition. All these results show that the gold-chloroquine binding can lead to compounds with specific properties that could make them useful in the treatment of some inflammatory diseases.
Chemistry Center, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela. mnavarro@ivic.ve
Maribel
M
Navarro
Flor
F
Vásquez
Mait
M
Velásquez
Rafael
R
Medina
Ronald
R
Reggio
German
G
Fraile
D000255:Adenosine Triphosphate / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System; D002738:Chloroquine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006046:Gold / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006046:Gold; D002738:Chloroquine; D000255:Adenosine Triphosphate; D013755:Tetradecanoylphorbol Acetate