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.