Chemical speciation studies in relation to aluminium metabolism and toxicity

Abstract

As a detrimental element, aluminium poses a threat to human health at two levels of contamination: (i) environmental (dietary) levels, due mainly to the release of natural stores by acid rains but also to industrial contamination (chronic intoxication), and (ii) therapeutic levels, which affect patients receiving high doses of Al-containing drugs (acute intoxication). In both cases, the bioavailability of aluminium conditions its degree of potential toxicity. Aluminium bioavailability directly depends on the chemistry of the A1 3+ ion in vivo. In particular, the high charge-to-radius ratio of A1 3+, which determines its specific affinity for oxygen donors, is at the origin of its detrimental effects on macromolecular biological structures. In this context, a better understanding of the metabolism of aluminium and of its influence on physiological processes requires a knowledge of its distribution in the main biofluids. This is the raison d'être of speciation, either directly through experimental analysis of biological samples, or indirectly via calculations based on conditional constant analysis or computer simulation models. To realize the importance of speciation with respect to the challenge posed by aluminium toxicity, it is important to have a knowledge of all the biological implications of Al-ligand interactions in vivo. For this reason, this article begins with a review of the roles of Al-ligand interactions in aluminium metabolism and toxicity. Contributions of speciation to the understanding of the relevant problems are then treated in perspective with this background, including experimental speciation and computer-aided speciation. In spite of numerous attempts to build reliable simulation models of the distribution of aluminium in the main biofluids (e.g. blood plasma), no definitive results have yet been reached, and the few data available in this field have been established mainly on a conditional constant basis. In general, there is a sharp contrast between the recent advances made by physiologists and toxicologists and the paucity of data obtained by coordination chemists likely to interpret the corresponding phenomena.