M. Favarato

Aluminum(III) influences the permeability of the blood-brain barrier to [14C]sucrose in rats

To determine the influence of the metal coordination sphere on the permeability of the blood-brain barrier (BBB), rats were injected intraperitoneally with aluminum lactate (Al(lact)3), aluminum acetylacetonate (Al(acac)3), aluminum maltolate (Al(malt)3) at pH 7.5, or with physiological saline. Two h after each treatment, [14C]sucrose physiological saline solution was injected in animals, and the radioactivity was measured in 5 brain regions (cerebral cortex, mesencephalon, diencephalon, medulla-pons, cerebellum). Radioactivity was significantly elevated in brains from animals treated with Al(malt)3 (hydrolytically stable and hydrophilic), and with Al(acac)3 (hydrolytically stable and lipophilic) but not with Al(lact)3. Time-course study carried out at 2, 4 and 24 h with different aluminum compounds showed a persistent radioactivity 24 h after treatment only in the brain from animals treated with Al(acac)3. Morin stain localized AlIII only in neurons from animals treated with Al(acac)3. These findings indicate that AlIII alters the BBB function in the rat either permanently or transiently depending on the physiochemical properties of the metal coordination sphere. Implications of these results, in terms of AlIII as a potential toxic factor in humans, are considered and discussed.

Crystal and molecular structures of diaqua(nitrilotriacetato)aluminium(III) and di-µ-hydroxo-bis(nitrilotriacetato)dialuminate(III) dianion

The crystal structures of [Al(nta)(H2O)2]·(CH3)2CO·H2O (1) and [Al(H2O)2][Al2(nta)2(µ-OH)2]-OH·3H2O (2)(nta = nitrilotriacetate) were determined by X-ray crystallography and refined to R= 0.043 [(1)] and 0.045 [(2)]. In both cases the ligating behaviour of nta3– is uncomplicated, i.e. quadridentate and non-bridging, and the geometry around AlIII is distorted octahedral, owing to the geometric requirements of the nta3– ligand. Compound (2) contains dimeric groups in which two Al–nta moieties are joined by two OH bridges; the Al ⋯ Al distance is equal to 2.842(2)A. Both crystal lattices are stabilized by significant intermolecular hydrogen bonds.

Effects of aluminum speciation on murine neuroblastoma cells

Murine neuroblastoma cells behave differently in the presence of Al(acac)3 [acac = 2,4-pentanedionate; acetylacetonate] or Al(malt)3 [malt = 3-hydroxy, 2-methyl, 4-pyronate; maltolate] with respect to Al(lac)3 [lac = 2-hydroxypropionate; lactate]. Thus, a remarkable cytotoxic effect was observed in the first case; on the contrary, an evident cytostatic and neuritogenic effect was produced by aqueous Al(lac)3. The hydrolytically stable complexes Al(acac)3 and Al(malt)3 were both toxic in the concentration range of 0.10-0.30 and 0.10-0.50 mM, respectively, over 24 h. In contrast with this behavior Al(lac)3 displayed a potent cytostatic activity with induction of neurites at 0.2-10 mM. Al(OH)3 manifested biological effects comparable to those exhibited by Al(lac)3. AlPO4 was also cytostatic and led to a morphological differentiation of the neuroblastoma cells, qualitatively different from that elicited by Al(lac)3. The morphological effects induced by Al(lac)3, Al(OH)3, and AlPO4 were irreversible.

A neutral lipophilic compound of aluminum(III) as a cause of myocardial infarct in the rabbit.

Intravenous administration of aluminum(III) in the form of the hydrolytically stable and moderately lipophilic complex acetylacetonate in the rabbit a severe pathological picture, the most significant feature of which is the occurrence of a myocardial infarct.

Differential aluminum lactate toxicity in rabbits using either aqueous solutions or liposomal suspensions

The present paper deals with the toxic effects of aluminum lactate (Al(lact)3) in rabbits. Experimental animals were injected with 6.2 mg of Al(III) as Al(lact)3 aqueous solutions at neutral pH for 21 days. Histological examination showed different pathological lesions to the myocardial tissue, spleen, kidney and liver, with no relevant effects to lungs and CNS. On the contrary, rabbits injected with 60 micrograms of Al(III) as Al(lact)3 in a liposome suspension for 42 days showed a large infarctual zone in the spinal cord with the metal accumulation in the necrobiotic neurons. Pharmacological implications of these findings are also discussed.

A long-term toxicological investigation on the effect of tris(maltolate)aluminum(III) in rabbits

The toxicity of iv injected hydrophilic aluminum complex tris(maltolate)aluminum(III) was studied in New Zealand white rabbits for a period of time ranging from 5 to 63 wk. Animals were injected 3–5 times a week with 1 mL of 7.5 mM Al(malt)3 and one rabbit with a dose 10 times higher after 14 wk of treatment. Autopical examination was performed on all animals. Chemoclinical analysis (glucose, urea, creatinine, cholesterol, bilirubin, alanin aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyltransferase, LDH, CK, total protein, triglycerides, and Ca2+) gave no variation in treated animals with respect to the control. The toxicological data show a moderate systemic general toxicity at doses far higher than those used in similar previous experiments using Al(acac)3 (acac=2,4 pentanedionate), a hydrolytically stable and more lipophilic aluminum(III) complex (1). The diversity of behavior is discussed in terms of metal speciation as well as respect to the thermodynamic and kinetic properties of the two complexes in aqueous solution. The toxicological model presented here emphasizes that neutral, water compatible aluminum(III) complexes are to be considered as promising tools for toxicological experiments providing biological models of human pathologies.

Gallium distribution in several human brain areas

Gallium is an element of increasing biological interest: It is involved in problems related to environmental pollution (Ga compounds are used in electronics industry) and to clinical treatments (Ga radionuclides are employed to detect neoplastic lesions). Moreover, since its chemical behavior is similar to that of aluminum, gallium could play a role in the health effects attributed to this element.Data on naturally occurring Ga levels in human samples from healthy subjects are scanty; regarding the brain, the only reliable values available in the literature were published by Hamilton in 1972/73. In this work, the gallium distribution in several human brain areas, evaluated by radiochemical neutron activation analysis (RNAA), was found to be dishomogeneous. The element concentration determined in dry samples was, in any case, lower than the ppb level.