Differential toxicity of novel aluminium compounds in hippocampal culture

The dependence of aluminium (Al) toxicity on its chemical form has been implicated in previous studies, but the complex chemistry of Al in solutions of biological preparations has hampered a reliable assessment. Here, we assessed the toxicity of select and pure Al(III) citrate compounds, well-characterized at physiological pH, and compared it with Al from standard solution (in HCl). Cell death rates of neurones and glia were established in hippocampal cultures following 3 h incubations in a HEPES-buffered solution and 24 h incubations in full culture medium. Overall, Al toxicity was found to vary considerably between compounds, with duration of exposure, medium type, and cell type as factors. While Al (from atomic absorption standard solution) induced the highest levels of cell death, AlCit1, ((NH 4) 5[Al(C 6H 4O 7) 2]·2H 2O) was the most toxic citrate compound, and affected viability of neurones more than glia (viability at 500 μM/3 h—neurones: 40%; glia: 60%). AlCit2 (K 4[Al(C 6H 4O 7)(C 6H 5O 7)]·4H 2O) did not show any toxicity after 3 h, but severe toxicity after 24 h in both cell types (viability at 500 μM/24 h—neurones: 50%, glia: 30%). AlCit3 ((NH 4) 5[Al 3(C 6H 4O 7) 3(OH)(H 2O)]·(NO 3)·6H 2O), exhibited a cell type specific toxicity profile, and only affected neuronal viability at both time points (neuronal viability at 500 μM/3 h: 20%). The medium type and presence of serum (FBS) was also found to contribute to the toxicity pattern, with serum providing partial protection. Since the Al(III) compounds introduced here are assumed to form in vivo, our data raise further awareness for the toxicity of Al(III) in general, and for the importance of Al speciation and cell type specific actions in its toxicity.