{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:32:05Z","timestamp":1791426725488,"version":"4.3.3"},"reference-count":0,"publisher":"Wiley","issue":"5-6","license":[{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"content-version":"vor","delay-in-days":2191,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"content-version":"vor","delay-in-days":2191,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Metal-Based Drugs"],"published-print":{"date-parts":[[1994,1]]},"abstract":"<jats:p>Leads to the cellular effects of the anti\u2010arthritic gold complexes may come from \nthe determination of their metabolism by target cells and, possibly, cells in the immediate\nenvironment of the target cells. Polymorphonuclear leukocytes (PMN) and mononuclear cells\n(monocytes and lymphocytes) are present in inflamed joints of patients with rheumatoid arthritis and\nthese cells have been widely used in pharmacological studies on the gold complexes. It is\nsuggested that the cellular effects of the gold complexes are mediated by the production of\naurocyanide. According to this hypothesis, PMN metabolize small quantities of thiocyanate to\ncyanide which, in turn, converts gold complexes, such as aurothiomalate, to aurocyanide\n(dicyanogold(I)) which inhibits the functions of PMN and other cells. There is now considerable\nevidence for this hypothesis from <jats:italic>in vitro<\/jats:italic> studies but there is little <jats:italic>in vivo<\/jats:italic> work to back up the\nhypothesis. One of the few <jats:italic>in vivo<\/jats:italic> studies which tested the hypothesis involved the examination\nof the activity of aurothiomalate in the treatment of polyarthritis in Hooded Wistar rats. Activity of\naurothiomalate is only shown in animals which received thiocyanate. Hydrogen cyanide is a\nconstituent of cigarette smoke and the aurocyanide formed by the interaction with gold complexes\nand inhaled hydrogen cyanide rapidly diffuses into red blood cells. Because of the metabolism of\nhydrogen cyanide to thiocyanate in the liver, there are higher plasma levels of thiocyanate in\nsmokers than in non\u2010smokers. Smokers may have a greater incidence of side effects than non\u2010smokers\nbut there appears to be little difference in therapeutic response, possibly because there is\nsufficient thiocyanate in extracellular fluid, even in non\u2010smokers, to support the conversion of gold\ncomplexes to aurocyanide. The relationship between the metabolism and effects of the orally\nactive gold complex, auranofin are less clear. Auranofin itself is taken up by cells with the loss of the\nligands bound to gold while its inhibitory activity against the oxidative burst of PMN decreases with\nincreasing cell density. For example, the lucigenin\u2010dependent chemiluminescence of 10<jats:sup>6<\/jats:sup> PMN\/ml\nis 46 percent of control at 0.5 \u03bcM auranofin but only 2.2 percent in 2.10<jats:sup>5<\/jats:sup> PMN\/ml in the presence\nof the same concentration of auranofin. A potentially active gold complex is a plasma component\nwhich is taken up by red blood cells.<\/jats:p>","DOI":"10.1155\/mbd.1994.395","type":"journal-article","created":{"date-parts":[[2007,3,14]],"date-time":"2007-03-14T12:33:53Z","timestamp":1173875633000},"page":"395-404","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The Cellular Metabolism and Effects of Gold Complexes"],"prefix":"10.1155","volume":"1","author":[{"given":"Garry G.","family":"Graham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. David","family":"Champion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Ziegler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[1994,1]]},"container-title":["Metal-Based Drugs"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/archive\/1994\/681372.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/MBD.1994.395","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T13:52:36Z","timestamp":1723470756000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/MBD.1994.395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,1]]},"references-count":0,"journal-issue":{"issue":"5-6","published-print":{"date-parts":[[1994,1]]}},"alternative-id":["10.1155\/MBD.1994.395"],"URL":"https:\/\/doi.org\/10.1155\/mbd.1994.395","archive":["Portico"],"relation":{},"ISSN":["0793-0291","1687-5486"],"issn-type":[{"value":"0793-0291","type":"print"},{"value":"1687-5486","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,1]]},"assertion":[{"value":"2000-01-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}