Reduction of toxicity in the premature neonate addociated with aluminum as a contaminant of total parenteral nutrition solution

by Srisung, Sujittra

Aluminum (Al) is the third most common element in the Earth’s crust. It is widely consumed in water, foods, and drugs. However, in humans, the uptake of aluminum into the body and its deposition in tissues has been linked to conditions of medical concern, including many neurological disorders such as dialysis dementia, Alzheimer’s disease, Parkinson’s dementia and Down’s syndrome. Premature neonates who receive intravenous feeding (TPN) are at a high risk for Al toxicity because the TPN solutions are contaminated with Al3+, which is not excreted effectively due to poor kidney development in these patients. The FDA has recommended regulations to limit the Al3+ contaminant in TPN solutions, but the aluminum is very difficult to remove. Thus, the development of an immobilized hydroxamate chelator to remove the Al3+ from key components of TPN solutions is an important goal. In this work, the complexation of Fe3+ and Al3+ by new ligands containing one, two and three hydroxamic acid groups has been studied by potentiometric titration and UV-vis spectroscopy to evaluate the metal-ligand complex stabilities of these new ligands. The binding of the divalent metal ions Cu2+, Ni2+, Zn2+, Ca2+ and Mn2+ by these ligands has also been evaluated by potentiometric titration. The trihydroxamate ligand shows a high affinity for Al3+ and Fe3+ and high selectivity for trivalent ions over divalent ions. Because aqueous calcium gluconate is the component of TPN solutions that contributes most of the aluminum contamination, the stability constant of Al-gluconate was also determined by spectrophotometric competition. We have immobilized the trihydroxamate ligand, 2,2,2-THA, on a polystyrene resin and studied the ability of this resin to remove Al3+ from solutions by spectrophotometric competition. The resin can easily remove Al3+ from buffered aqueous solutions. However, the Al-binding affinity of the resin-bound ligand is less than that of the free ligand. As a result, the resin is not very effective for the removal of Al3+ from gluconate solutions. i