Are some major in vivo effects of gold related to microenvironments of decreased selenium?

Dillard, Cora J.; Tappel, Al L.

doi:10.1016/0306-9877(86)90101-5

Cited by 9 publications

(11 citation statements)

References 41 publications

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“…It should be noted that the dosage used exceeds that given to rheumatoid arthritis patients by a factor Desired and Undesired Effects on the Immune System of at least 30. This difference in dosage was chosen because of the greater metabolic activity in mice compared to men and because previous investigations had shown that this dosage induced immunologic side-effects in mice similar in those seen in men (6,(23)(24)(25).…”

Section: Gold Kinetics In Humans and Mice Under Long-term Treatment Wmentioning

confidence: 99%

“…In all three tissues studied, especially the spleen, strain DBA/2 contained lower gold levels than strains C57BL/6 and A.SW. Whereas the latter two strains are known to be susceptible to the adverse immunologic side-effects of Na2Au(I)TM, strain DBA/2 is resistant (6,(23)(24)(25)). An observation made in all three mouse strains was that the concentration of gold in the spleen, an organ of the immune system, steadily increased until week 10 or 12.…”

Section: Gold Kinetics In Humans and Mice Under Long-term Treatment Wmentioning

confidence: 99%

“…At least some of the immunopathologic side-effects seen in man also develop in susceptible mouse strains treated with weekly intramuscular injections of Na2Au(I)TM (Table 1). Equimolar injections of the carrier disodium thiomalate (Na2TM), by contrast, fail to induce any of these anormalities (6,23,48). As in humans, genes linked to the MHC as well as non-MHC genes are involved in the immunologic susceptibility of mice to Na2Au(I)TM (23).…”

Section: Biooxidation Of Au(i) To Au(lll) In Vivomentioning

confidence: 99%

“…By contrast, equimolar amounts of Au(lll) salts readily induced a T cell-dependent PLN reaction. The PLNA is an in vivo test system for measuring specific T cell reactions toward chemicals of low molecular weight (6,(51)(52)(53).…”

Section: Biooxidation Of Au(i) To Au(lll) In Vivomentioning

confidence: 99%

“…Eventually adverse immune reactions necessitate discontinuation of gold therapy in up to one-third of patients (3)(4)(5). The immunopathologic alterations developing under gold therapy (6) are summarized in Table 1. Although antirheumatic gold drugs have been successfully used for almost six decades, the mechanism of action underlying their beneficial and their adverse effects are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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The Antirheumatic Drug Gold, a Coin With Two Faces: AU(I) and AU(III).Desired and Undesired Effects on the Immune System

et al. 1994

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Three new findings are reviewed that help to understand the mechanisms of action of antirheumatic Au(I) drugs, such as disodium aurothiomalate (Na2Au(I)TM): (i) We found that Na2Au(I)TM selectively inhibits T cell receptor (TCR)-mediated antigen recognition by murine CD4+ T cell hybridomas specific for antigenic peptides containing at least two cysteine residues. Presumably, Au(I) acts as a chelating agent forming linear complexes (Cys-Au(I)-Cys) which prevent correct antigen-processing and/or peptide recognition by the TCR. (ii) We were able to show that Au(I) is oxidized to Au(III) in phagocytic cells, such as macrophages. Because Au(III) is re-reduced to Au(I) this may introduce an Au(I)/Au(III) redox system into phagocytes which scavenges reactive oxygen species, such as OCl- and inactivates lysosomal enzymes. (iii) Pretreatment with Au(III) of a model protein antigen, bovine ribonuclease A (RNase A), induced novel antigenic determinants recognized by CD4+ T lymphocytes. Analysis of the fine specificity of these ‘Au(III)-specific’ T cells revealed that they react to RNase peptides that are not presented to T cells when the native protein, i.e., not treated with Au(III), is used as antigen. The T cell recognition of these cryptic peptides did not require the presence of gold. This finding has important implications for understanding the pathogenesis of allergic and autoimmune responses induced by Au(I) drugs. Taken together, our findings indicate that Au(I) and Au(III) each exert specific effects on several distinct components of macrophages and the subsequent activation of T cells; these effects may explain both the desired anti-inflammatory and the adverse effects of antirheumatic gold drugs.

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Section: Gold Kinetics In Humans and Mice Under Long-term Treatment Wmentioning

confidence: 99%

Section: Gold Kinetics In Humans and Mice Under Long-term Treatment Wmentioning

confidence: 99%

Section: Biooxidation Of Au(i) To Au(lll) In Vivomentioning

confidence: 99%

Section: Biooxidation Of Au(i) To Au(lll) In Vivomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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