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Methods Find Exp Clin Pharmacol. 1997 Nov;19(9):599-604.

Chronic aluminum intoxication in rats: dose-dependent morphological changes.

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Department of Human Physiology and Physiological Chemistry, University of Durban-Westville, South Africa.


The objective of the study was to evaluate the chronic cytotoxic effect of very low nontoxic aluminum (Al) in the drinking water of rats. The control group (10 rats) received deionized water, whereas the two experimental groups (10 rats each) received Al in a dose of 5 mg and 20 mg/kg bw/day, respectively. Al was applied in their drinking water during the 6-month duration of the study. Light and electron microscopy (EM) was performed on several body tissues (i.e., kidney, liver muscle, brain). The results showed distinct dose-dependent changes in kidney and brain. In tubulo-interstitial part of the kidney many proximal tubules were hyperdilated. Their cells were swollen and the microvilli were largely lost. Atrophy of some tubules, surrounded by focal areas of interstitial fibrosis was also observed. Some of the glomeruli were undergoing partial sclerosis and in many focal mesangial hypercellularity was found. No distinct morphological changes in other peripheral tissues were observed. In brain, most pronounced changes were observed in hippocampus: they include spongioform changes in pyramidal layer, nuclear deformity and presence of vaculoes in the nuclei. Neurofibrillary degeneration, similar to neurofibrillary tangles in Alzheimer's disease, was also observed. It can thus be concluded that despite very low gastrointestinal absorption (less than 1%), Al in drinking water might accumulate in the long term in vital organs such as kidney and brain, with distinct cytotoxic and neurotoxic effects.

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