Differential toxicity of aluminum salts in human cell lines of neural origin: Implications for neurodegeneration

Aluminium is highly oxophilic and its minerals are usually found surrounded by six oxygen atoms. A role for the metal has been established in dialysis encephalopathy and Al-induced osteomalacia. The metal has been implicated in Alzheimer's disease but tire issue is at present controversial. Human cell lines of neural al origin were utili ed to study the effect of lipophilic aluminium acetylacetonate and non lipophilic aluminium sulfate on cell proliferation and viability. Although analysis of Al species in the cell culture media demonstrated that there are positively charged Al species present in solutions prepared with both Al salts, only the aluminium acetylacetonate salt caused changes in cell proliferation and viability. Therefore, the lipophilic nature of the organic Al salt is a critical determinant of toxicity. The effect of aluminum acetylacetonate was dose-dependent and time-dependent. Neuroblastoma (SK-IV-SH) cells were mol-e susceptible to deceased cell proliferation although the lipophilic Al salt tvas more toxic to the glioblastoma (T98G) cells. While the toxicity of aluminum acetylacetonate was ir inhibited in the T98G cells by the addition of phosphate, the same treatment did nor reverse cell death in the SK-N-SH cells. Thus, the mechanism of Al toxicity appears to be different in the two cell lines. It is possible that the principal neurotoxic target of the metal is glial and when these cells are in a compromised state, this may secondarily impact the neuronal population and thus eventually, lend to neurodegeneration. (C) 2001 Elsevier Science Inc. All rights reserved.