Conditional pharmacology/toxicology V: ambivalent effects of thiocyanate upon the development and the inhibition of expe
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Inflammopharmacology
REVIEW
Conditional pharmacology/toxicology V: ambivalent effects of thiocyanate upon the development and the inhibition of experimental arthritis in rats by aurothiomalate (MyocrysinÒ) and metallic silver Michael Whitehouse • Desley Butters Barrie Vernon-Roberts
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Received: 24 January 2013 / Accepted: 26 April 2013 / Published online: 19 May 2013 Ó Springer Basel 2013
Abstract This article discusses the bizarre and contrary effects of thiocyanate, the major detoxication product of hydrogen cyanide inhaled from tobacco smoke or liberated from cyanogenic foods, e.g. cassava. Thiocyanate both (1) promotes inflammatory disease in rats and (2) facilitates the anti-inflammatory action of historic metal therapies based on gold (Au) or silver (Ag) in three models of chronic polyarthritis in rats. Low doses of nanoparticulate metallic silver (NMS) preparations, i.e. zerovalent silver (Ag°) administered orally, suppressed the mycobacterial (‘adjuvant’)-induced arthritis (MIA) in rats. Similar doses of cationic silver, Ag(I), administered orally as silver oxide or soluble silver salts were inactive. By contrast, NMS only inhibited the development of the collagen-induced arthritis (CIA) and pristane-induced arthritis (PIA) in rats when thiocyanate was also co-administered in drinking water. These (a) arthritis-selective and (b) thiocyanate-inducible
effects of Ag° were also observed in some previous, and now extended, studies with the classic anti-arthritic drug, sodium aurothiomalate (ATM, MyocrisinÒ) and its silver analogue (STM), administered subcutaneously to rats developing the same three forms of polyarthritis. In the absence of either Ag° or ATM, thiocyanate considerably increased the severity of the MIA, CIA and PIA, i.e. acting as a pro-pathogen. Hitherto, thiocyanate was considered relatively harmless. This may not be true in rats/people with immuno-inflammatory stress and concomitant leukocyte activation. Collectively, these findings show how the drug action of a xenobiotic might be determined by the nature (and severity) of the experimental inflammation, as an example of conditional pharmacology. They also suggest that an incipient toxicity, even of normobiotics such as thiocyanate, might likewise be modulated beneficially by well-chosen xenobiotics (drugs, nutritional supplements, etc.), i.e. conditional toxicology (Powanda 1995). Thus, both the disease and the environment may determine (1) the therapeutic action and/or (2) adverse effect(s) of xenobiotics—and even some normobiotics.
Special issue: Dedicated to the ‘‘Life and work of Professor Barrie Vernon-Roberts’’
Keywords Adjuvant arthritis Aurothiomalate Collagen arthritis (nanoparticulate) Metallic silver Pristane arthritis Thiocyanate
M. Whitehouse B. Vernon-Roberts Discipline of Pathology, School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia M. Whitehouse D. Butters Therapeutics Research Unit, Department of Medicine, University of Queensland, Princess Alexandra Hospital, Woolloongabba, Brisbane,
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