Inhibition of synovial fluid lysosomal glycosidases by anti-Arthritic gold preparations

Abstract

The ability of currently available anti-arthritic gold preparations to inhibit lysosomal glycosidases from rheumatoid synovial fluid and normal human serum was studied in vitro.It was shown that these preparations differ markedly in their ability to inhibit the enzymes. Gold thioglucose (Solganal) did not inh~it ~-glucuronidase ~-GLUC), ~-Nacetylglucosaminldase (t-NAG) or hyaluronidasc (HASE). Chloro(triethylphosphine)gnld (SK&F 36914) was a potent inhibitor oft-NAG only. Sodium aurothlomalate (Myochrysine and sodium 3-aurnthio-2-prupanol-l-snlphonate (Allyoehrysine) were inhibiturs of all three enzymes, notably #-GLUC.Kinetic analysis of inhibition by aurothiomalate demonstrated apparent competitive inhibition with fl-GLUC, but non-competitive inhibition with HASE and t-NAG fl-GLUC was also strongly inhibited by silver and copper thiomalates.

Effect ofin vivo administration of gold sodium thiomalate on rat macrophage function

“…As was confirmed in this study, gold thiomalate can inhibit fl-glucuronidase [24,[26][27][28][29]32] and acid phosphatase [26,31,32] in vitro. The concentrations required, however, are far in excess of those maintained in vivo in plasma either during chrysotherapy [52] or, similarly, during the weekly injection schedule of this study.…”

“…Direct addition of gold to isolated cells can cause an increase in F e receptor activity [171, inhibition of monocyte to macrophage differentiation [18], inhibition of accessory cell function in humoral and cellular immune mechanisms [19], reduction of monocyte chemotaxis [20], and diminished capacities for pinocytosis [21], phagocytosis [21][22][23], adherence [22] and digestion [18]. Further, gold has inhibitory effects on lysosomal enzymes [24][25][26][27][28][29][30][31][32] and prostaglandin formation [33] in vitro. However, the relevance of this information to the in vivo circumstance is uncertain.…”

Effects of dissolucytotic gold ions on recovering brain lesions

“…Autometallographic (AMG) studies have revealed that gold ions originating from gold salts have their metabolic end station in the lysosomal compartment, and the excess accumulation of gold containing macromolecules causes rupture of the lysosomal membrane (Davies et al 1971, Burkhardt et al 1978Danscher 1981Danscher , 1991Brunk et al 1997;Møller-Madsen et al 1984). Gold ions resulting from gold salts have also been shown to be transported over the placental barrier and into the human embryo (Møller-Madsen et al 1987) and to accumulate in the dorsal root ganglia (Schiønning et al 1992).…”

Effects of gold sodium thiomalate on interferon stimulation of C2 synthesis and HLA–DR expression by human monocytes

“…Gold salts decrease monocyte secretory and phagocytic capacity (23)(24)(25), impair monocyte chemotaxis and migration (26,27), and inhibit lymphocyte proliferation to antigens and mitogens (28,29). C1 and several lysosomal enzymes are inactivated by gold salts (30)(31)(32). These effects serve to down-regulate the exuberant inflammatory response characteristic of active RA.…”