The biological speciation and toxicokinetics of aluminum.

Abstract

This review discusses recent literature on the chemical and physiological factors that influence the absorption, distribution, and excretion of aluminum in mammals, with particular regard to gastrointestinal absorption and speciation in plasma. Humans encounter aluminum, a ubiquitous yet highly insoluble element in most forms, in foods, drinking water, and pharmaceuticals. Exposure also occurs by inhalation of dust and aerosols, particularly in occupational settings. Absorption from the gut depends largely on pH and the presence of complexing ligands, particularly carboxylic acids, with which the metal can form absorbable neutral aluminum species. Uremic animals and humans experience higher than normal body burdens of aluminum despite increased urinary clearance of the metal. In plasma, 80-90% of aluminum binds to transferrin, an iron-transport protein for which receptors exist in many tissue. The remaining fraction of plasma aluminum takes the form of small-molecule hydroxy species and small complexes with carboxylic acids, phosphate, and, to a much lesser degree, amino acids. Most of these species have not been observed in vivo but are predicted from equilibrium models derived from potentiometric methods and NMR investigations. These models predict that the major small-molecule aluminum species under plasma conditions are charged and hence unavailable for uptake into tissues.

Metal deposition in calcific uremic arteriolopathy

“…Increased dietary intake in the context of poor urinary excretion could have contributed to tissue aluminum load. 27 In some patients, parenteral nutrition, 10,28 or medications, 29 could also be an important source of aluminum accumulation. Other speculative sources of aluminum elevation in tissue include: a) systemic inflammation and consequent low serum transferrin such as is in CUA patients may result in competition for transferrin binding sites between iron and aluminum, resulting in aluminum deposition, 31 or b) hyperparathyroidism may result in high bone turnover and mobilization of aluminum from bone stores (even from aluminum deposits from long ago).…”

Dietary protein restriction causes modification in aluminum-induced alteration in glutamate and GABA system of rat brain

“…Reports available on interaction between aluminum and glutamate are controversial. Glutamate is a potential binder of aluminum in physiological solutions [20]. Jones and Oorschot [21] had reported the absence of aluminum-induced conformational changes in tau protein when applied in combination with glutamate.…”

“…But the γ-aminobutyric acid transaminase (GABA-T; the major GABA degrading enzyme) activity was found to alter in a region specific and dietary protein specific manner (Table 4). Glutamate was reported to be increased in the brain of protein-restricted rats [9] and it is a specific binder to aluminum ion [20,28]. Hence, alterations in GAD and GABA-T activities observed in normal dietary protein group in response to aluminum exposure were reversed or tended to neutralized in protein-restricted group and glutamate may have played an important role in this.…”

Response of regional brain glutamate transaminases of rat to aluminum in protein malnutrition

“…It has been reported that aluminum impairs the glutamatergic neurotransmission [8] and mediates glutamate-induced neurotoxicity in organotypic cultures [9]. On the other hand, glutamate is an important metabolic intermediate of the brain and it has potential aluminum binding capacity [10]. In our earlier studies, we have shown that aluminum causes alteration in glutamate levels and glutamate α-decarboxylase activities of different brain regions [11].…”