Proceedings of the 3rd International Conference on Gold and Silver in MedicineView this Special Issue
Garry G. Graham, G. David Champion, John B. Ziegler, "The Cellular Metabolism and Effects of Gold Complexes", Metal-Based Drugs, vol. 1, Article ID 681372, 10 pages, 1994. https://doi.org/10.1155/MBD.1994.395
The Cellular Metabolism and Effects of Gold Complexes
Leads to the cellular effects of the anti-arthritic gold complexes may come from the determination of their metabolism by target cells and, possibly, cells in the immediate environment of the target cells. Polymorphonuclear leukocytes (PMN) and mononuclear cells (monocytes and lymphocytes) are present in inflamed joints of patients with rheumatoid arthritis and these cells have been widely used in pharmacological studies on the gold complexes. It is suggested that the cellular effects of the gold complexes are mediated by the production of aurocyanide. According to this hypothesis, PMN metabolize small quantities of thiocyanate to cyanide which, in turn, converts gold complexes, such as aurothiomalate, to aurocyanide (dicyanogold(I)) which inhibits the functions of PMN and other cells. There is now considerable evidence for this hypothesis from in vitro studies but there is little in vivo work to back up the hypothesis. One of the few in vivo studies which tested the hypothesis involved the examination of the activity of aurothiomalate in the treatment of polyarthritis in Hooded Wistar rats. Activity of aurothiomalate is only shown in animals which received thiocyanate. Hydrogen cyanide is a constituent of cigarette smoke and the aurocyanide formed by the interaction with gold complexes and inhaled hydrogen cyanide rapidly diffuses into red blood cells. Because of the metabolism of hydrogen cyanide to thiocyanate in the liver, there are higher plasma levels of thiocyanate in smokers than in non-smokers. Smokers may have a greater incidence of side effects than non-smokers but there appears to be little difference in therapeutic response, possibly because there is sufficient thiocyanate in extracellular fluid, even in non-smokers, to support the conversion of gold complexes to aurocyanide. The relationship between the metabolism and effects of the orally active gold complex, auranofin are less clear. Auranofin itself is taken up by cells with the loss of the ligands bound to gold while its inhibitory activity against the oxidative burst of PMN decreases with increasing cell density. For example, the lucigenin-dependent chemiluminescence of PMN/ml is 46 percent of control at 0.5 μM auranofin but only 2.2 percent in PMN/ml in the presence of the same concentration of auranofin. A potentially active gold complex is a plasma component which is taken up by red blood cells.
Copyright © 1994 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.