Aluminum speciation studies in biological fluids. Part 4. A new investigation of aluminum–succinate complex formation under physiological conditions, and possible implications for aluminum metabolism and toxicity

Abstract

Previous in vivo studies devoted to the capacity of succinate to influence aluminum metabolism have led to apparent contradictory results. Understanding the mechanisms that lie behind such discrepancies requires a knowledge of aluminum–succinate interactions at the molecular level. In the absence of possible direct analysis of the ultrafiltrable fraction of aluminum in vivo, computer simulations can help quantify the mobilizing power of succinate towards aluminum in the main biofluids. Based on this technique, a first attempt to elucidate the above issue was made using especially determined aluminum–succinate formation constants. However, further investigations have led to reconsider the stoichiometry of the aluminum–succinate complexes characterized on that occasion. The present work deals with these new investigations. The results obtained confirm the great complexity of the aluminum–succinate system. No less than seven species, among which five polynuclear complexes, have been characterized in two series of independent experiments. New simulations indicate that succinate is expected to facilitate aluminum gastrointestinal absorption to a greater extent than initially predicted when the metal is administered as its trihydroxide, especially at high concentrations of the metal. In contrast, succinate is not able to significantly increase aluminum absorption when ingested concomitantly with aluminum phosphate. It is also confirmed that succinate cannot influence the fate of aluminum in blood plasma, which supports the view that the protective effect of succinate against aluminum toxicity in mice is not due to aluminum complexation.