Gold kinetics under long-term treatment with gold(I) disodium thiomalate: a comparison in three different mouse strains.
Following weekly i.m. injections of gold(I) disodium thiomalate (GST), mice of strains A.SW and C57BL/6 develop adverse immune reactions, whereas DBA/2 mice do not. We have studied the pharmaco-toxicokinetics of gold in these strains under chronic GST treatment. Our results indicate that the susceptible strains A.SW and C57BL/6 accumulate significantly higher gold concentrations in the liver and spleen compared to the resistant strain DBA/2. In the kidney of DBA/2 mice, gold concentrations persisted at a plateau level, whereas in A.SW and, particularly, C57BL/6 mice early peaks of gold concentrations were followed by a transient decrease, suggestive of tubular toxicity. Whereas splenic T and B cells failed to contain measurable gold concentrations in all three strains, splenic and peritoneal macrophages contained relatively high levels, more so in the susceptible strain C57BL/6 than in the resistant DBA/2 strain. This finding is consistent with the concept that macrophages play an important role in both the adverse and the beneficial effects of gold drugs.
Tonn
T
T
Division of Immunology, Heinrich Heine University Düsseldorf, Germany.
Goebel
C
C
Wilhelm
M
M
Gleichmann
E
E
D000818:Animals; D005260:Female; D006046:Gold / Q000493:pharmacokinetics*; D006052:Gold Sodium Thiomalate / Q000008:administration & dosage* / Q000633:toxicity; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013045:Species Specificity; D013054:Spectrophotometry, Atomic; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D006052:Gold Sodium Thiomalate; D006046:Gold