Experimental articular toxicity of aluminum compounds in vivo.
OBJECTIVE
To investigate the articular toxicity of 2 aluminum derivatives, one insoluble (hydroxide) and/or the other soluble (lactate), after a single administration in rabbits and rats.


METHODS
First, aluminum levels in plasma, urine, synovial tissue, liver and kidney were measured in saline treated rabbits and 1 to 2 days after an articular injection of 75 mg of aluminum compounds into their right knee. The methodology used was argon plasma emission spectrometry. Thereafter, the joint toxicity of aluminum lactate at the same dose regimen was evaluated for 2 days by a qualitative histological examination of synovial tissue and articular surfaces and a colorimetric assay (1,9-DMB) of patellar articular cartilage proteoglycan content. Secondly, the single injection 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 injection into rabbit knee, aluminum lactate largely distributed within the body while hydroxide remained locally. However, aluminum lactate resulted 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 superficial zones of tibial and femoral cartilages when patellar proteoglycan content remained unchanged. Aluminum hydroxide did not affect joint structures. In the air pouch experiment, aluminum lactate increased prostaglandin E2 (PGE2) levels from 3 to 10 h after its injection and less intensively leukotriene B4 (LTB4) levels after 6 h, in the absence of leukocytes migration into the cavity. In contrast, aluminum hydroxide increased leukocytes count in pouch-washout fluid from 3 to 24 h after its injection when PGE2 and LTB4 levels were little modified.


CONCLUSIONS
Although some differences attributable to dissimilarities in the experimental model used, aluminum compounds, even in a soluble form, may damage joint structures either directly or through stimulating the secretion of eicosanoids by synovial-like cells.
Chary-Valckenaere
I
I
Department of Rheumatology, URA CNRS 1288, Vandoeuvre-les-Nancy, France.
Fener
P
P
Jouzeau
J Y
JY
Netter
P
P
Payan
E
E
Floquet
J
J
Burnel
D
D
Kessler
M
M
Pourel
J
J
Gaucher
A
A
D017607:Aluminum Compounds / Q000633:toxicity*; D000536:Aluminum Hydroxide / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D002452:Cell Count; D015232:Dinoprostone / Q000032:analysis*; D005260:Female; D007719:Knee Joint / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D007773:Lactates / Q000493:pharmacokinetics / Q000633:toxicity; D019344:Lactic Acid; D007958:Leukocyte Count / Q000187:drug effects; D007975:Leukotriene B4 / Q000032:analysis*; D008297:Male; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013585:Synovitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
D017607:Aluminum Compounds; D007773:Lactates; D007975:Leukotriene B4; D019344:Lactic Acid; D000536:Aluminum Hydroxide; D015232:Dinoprostone