EXPERIMENTAL ARTICULAR TOXICITY OF ALUMINUM COMPOUNDS IN-VIVO

Objective. To investigate the articular toxicity of 2 aluminum derivat ives, one insoluble (hydroxide) and/or the other soluble (lactate), af ter a single administration in rabbits and rats. Methods. First, alumi num levels in plasma, urine, synovial tissue, liver and kidney were me asured in saline treated rabbits and I to 2 days after an articular in jection of 75 mg of aluminum compounds into their right knee. The meth odology used was argon plasma emission spectrometry. Thereafter, the j oint toxicity of aluminum lactate at the same dose regimen was evaluat ed for 2 days by a qualitative histological examination of synovial ti ssue and articular surfaces and a colorimetric assay (1,9-DMB) of pate llar articular cartilage proteoglycan content. Secondly, the single in jection of 50 mg of aluminum derivatives as an inducer of inflammation was studied in the rat subcutaneous air pouch, a model for a synovial -like space. Leukocytes and eicosanoids levels were measured in pouch washout fluids from 1 to 72 h after injection. Results. After injectio n into rabbit knee, aluminum lactate largely distributed within the bo dy while hydroxide remained locally. However, aluminum lactate resulte d in perivascular edema, sparse infiltration of inflammatory cells in the synovium and a hemorrhagic effusion. Proliferation of the synovial cell layer coexisted with an apparent loss of proteoglycan in superfi cial zones of tibial and femoral cartilages when patellar proteoglycan content remained unchanged. Aluminum hydroxide did not affect joint s tructures. In the air pouch experiment, aluminum lactate increased pro staglandin E(2) (PGE(2)) levels from 3 to 10 h after its injection and less intensively leukotriene B-4 (LTB(4)) levels after 6 h, in the ab sence of leukocytes migration into the cavity. In contrast, aluminum h ydroxide increased leukocytes count in pouch-washout fluid from 3 to 2 4 h after its injection when PGE(2) and LTB(4) levels were little modi fied. Conclusion. Although some differences attributable to dissimilar ities in the experimental model used, aluminum compounds, even in a so luble form, may damage joint structures either directly or through sti mulating the secretion of eicosanoids by synovial-like cells.