A long-term intravenous model of aluminum maltol toxicity in rabbits: tissue distribution, hepatic, renal, and neuronal cytoskeletal changes associated with systemic exposure.

We studied the toxicity of an intravenously injected, water-soluble aluminum complex (aluminum maltol) in 20 young adult male New Zealand white rabbits over a period of 8 to 30 weeks. Sixteen rabbits injected with aluminum-free maltol and 15 untreated rabbits served as controls. Rabbits were injected three times per week with 75 mumol of aluminum maltol per injection, or a molar equivalent amount of maltol alone, through an indwelling jugular catheter. Liver contained the highest concentrations of aluminum among the aluminum maltol-treated rabbits, and aluminum accumulation was correlated with the appearance of periportal multinucleated giant cells in 13 of 20 rabbits. These cells stained positively for aluminum when a fluorescent (Morin) stain was applied to tissue from rabbits with a high concentration of aluminum in the liver. Proximal renal tubular necrosis or atrophy was found in 15 of 20 aluminum maltol-treated rabbits but not in maltol-treated and untreated controls. Renal tubules in rabbits with acute proximal renal necrosis stained positively for aluminum. Neurofibrillary tangles, immunoreactive with a monoclonal antibody to the 200-kDa subunit of neurofibrillary protein, were observed in the oculomotor nucleus of 3 aluminum maltol-treated rabbits (treated for 12, 20, and 29 weeks), but in none of the two groups of controls. These tangles were present in 3 of 10 aluminum-treated rabbits in which the nucleus was located. None of the 17 animals in both control groups in which the nucleus was found demonstrated tangles. A slight increase in brain tissue aluminum concentration was confirmed by an electrothermal atomic absorption spectrophotometric method. There were no specific findings in heart or lung tissue from aluminum-treated rabbits, although the aluminum content of these tissues was 10 to 20 times greater than control values. This model should be useful for investigating the effects of systemic exposure to high concentrations of solubilized aluminum.