Experimental aluminum pathology in rabbits: effects of hydrophilic and lipophilic compounds.

Aluminum lactate [Al(lact)3] (hydrophilic, hydrolytically unstable) and aluminum acetylacetonate [Al(acae)3] (lipophilic, hydrolytically stable) were tested as potential toxicants to rabbits upon IV administration both as aqueous solutions and as liposome suspensions. Both chemicals behaved as cardiotoxic agents when administered as aqueous solutions, but Al(acae)3 was at least two orders of magnitude more active than Al(lact)3. Al(acae)3, but not Al(lact)3, caused myocardial infarcts resembling those in humans (with contraction bands) at doses as low as 0.24 mg/kg body weight, as well as a prominent acanthocytosis. Al(lact)3, when administered as a liposome suspension, was about 300 times more toxic than in aqueous solution, although cardiac damage was not infarctual in character. Both chemical and physical speciation of aluminum(III) thus play an essential role in determining the toxicity of the metal.

Polybenzimidazole as a promising support for metal catalysis: morphology and molecular accessibility in the dry and swollen state

Polybenzimidazole (PBI) in beaded form (250-500 microm) has been characterized in the dry state by scanning electron microscopy (SEM), BET, and nitrogen porosimetry. In the swollen state, it has been characterized by inverse steric exclusion chromatography (ISEC) in tetrahydrofuran, toluene, and water, by ESR of TEMPONE (2,2,6,6-tetramethyl-4-oxo-1-oxypiperidine), and pulse field gradient spin echo (PGSE) NMR spectroscopy, toluene, in tetrahydrofuran, ethanol and water. The dry-state results are in good agreement with the ISEC results obtained in tetrahydrofuran, toluene, and water with regard to the 40-80 nm macroporosity. The swelling-dependent surface area and pore volume detected by ISEC in toluene and water reveal the amphiphilic nature of PBI.

Aluminum (III) induces alterations on the physical state of the erythrocytic membrane: an ESR evaluation.

The action of aluminum [Al(III)] as Al(acac)3 on erythrocytes causes biophysical effects such as osmotic fragility and echino-acanthocytes formation. In this paper, we present these effects in terms of variation of membrane fluidity, together with findings regarding conformational modifications of membrane proteins consequent to Al(III) exposure, as well as the effects on the mobility of the membrane protein bound sialic acid. To this end, we utilized ESR measurements of rabbits and humans erythrocytic ghosts after probing or labeling with suitable stable radicals used as spin probes or labels. Our results show that the lipophilic, hydrolytically stable toxicant Al(acac)3 causes a remarkable reduction of membrane fluidity in rabbit erythrocytes, an appreciable structural compacting effect on cytoskeletal and transmembrane proteins, as well as a reduction of rotational mobility of cell-surface sialic acid of human erythrocytes.

Tris acetylacetonate aluminium(III) induces osmotic fragility and acanthocyte formation in suspended erythrocytes.

Tris acetylacetonate aluminium(III) (Al(acac)3), dissolved in water, is effective in producing osmotic fragility in suspended erythrocytes in the concentration range of 0.034-0.34 mmol/l. Water solutions of Tris maltolate aluminium(III) (Al(malt)3) and aluminium lactate (Al(lac)3) are also effective but the dose-response behavior is less pronounced. Moreover, only Al(acac)3 induces a prominent generation of acanthocytes. The stronger effects of Al(acac)3 on membrane stability are attributed to the greater solubility of this complex in the cell membrane.

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.

Mass spectrometric behaviour of pentachlorophenyl beta-carbonylenolate phosphino nickel(II) complexes: An example of thermal generation of a nickel(III) species.

The mass spectral behaviour of pentachlorophenyl beta-carbonylenolate phosphino nickel(II) square planar complexes has been investigated under electron impact (EI) and field desorption (FD) conditions. The fragmentation has been interpreted on the basis of the B/E linked scans and mass-analysed ion kinetic energy (MIKE) techniques. The acetylacetonate diphenylphosphino complex was found to undergo a solid state reaction in the probe, which led to the generation in situ of a nickel(III) chloro complex. Careful control of instrumental conditions and computer-assisted EI measurements made it possible to characterize the addition products as [NiCl(C(6)Cl(5))(AcAc)PPh(2)Me] and to propose a mechanism for its solid state generation.

Alzheimer dementia and the aluminum hypothesis.

The possible involvement of environmental aluminum in the etiology of Alzheimer disease and of senile dementia of the Alzheimer type is supported by both direct and indirect relationships between some encephalopathies and the abnormal presence of aluminum(III) in human and animal brain tissues. Proposals for further biochemical, toxicological and analytical work are illustrated.

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

The toxicity of i.v. 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, gamma-glutamyl-transferase, 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.

Cardiotoxicity of the lipophilic compound aluminum acetylacetonate in rabbits.

Aluminum acetylacetonate was administered to New Zealand white rabbits as liposome preparations and was found to distribute approximately 1:1 between water and phosphatidylcholine dipalmitoyl vesicles. Biochemical monitoring proved that after 2 weeks of daily injection of 40 micrograms of Al(III) in the above form, the animals developed significant signs of cardiac suffering, evidenced by variations in lactic dehydrogenase and creatinine phospokinase. Histopathologic investigation revealed that aluminum acetylacetonate caused unambiguous myocardial infarcts, characterized by myocardial contraction bands. In contrast, injection of Al(III) as a simple salt (lactate, 20 mg/day for 3 weeks) gave a less severe myocardiopathy, certainly not infarctual. Aluminum acetylacetonate given to rabbits appears to be, to our knowledge, the only chemical tool able to mimic spontaneous infarction situations in humans.

Cross-linked polyvinyl polymers versus polyureas as designed supports for catalytically active M(0) nanoclusters. Part III. Nanometer scale structure of the cross-linked polyurea support EnCat 30 and of the Pd(II)/EnCat 30 and Pd(0)/EnCat 30NP catalysts.

The cross-linked polyurea support EnCat 30, its related macromolecular complex Pd(II)/EnCat 30 and its related Pd(0)/EnCat 30NP nanocomposite are thoroughly investigated with SEM, TEM, ISEC and ESR in the solid state (SEM and TEM) and swollen state in THF (ISEC and ESR). Pd(II)/EnCat 30 and its related Pd(0)/EnCat 30NP are obtained by microencapsulation of palladium acetate in a polyurea framework, which is formed upon hydrolysis/condensation of mixtures of multi-functional oligo-arylisocyanates in dichloroethane. Most remarkably, both Pd(II)/EnCat and Pd(0)/EnCat 30NP turn out to be far more (nano)porous and swellable materials than the blank polyurea matrix (EnCat 30). It is proposed that there is a strong nanostructural effect exerted by Pd(II) species due to its interaction with functional groups (amines stemming from the hydrolysis of the isocyanato groups or ureido groups belonging to the polymer chains) during the growth of the cross-linked polymer framework. As a consequence, the catalytic species in both Pd(II)/EnCat 30 and Pd(0)/EnCat 30NP are much more accessible to molecules diffusing from liquid phases in contact with the materials and, hence, are better catalysts than expected from the morphology of blank polyurea EnCat 30.

Reactivity of Al(III) with membrane phospholipids: a NMR approach.

The complexes Al(acac)3 (1) (acac = 2,4-pentanedionate) and Al(malt)3 (malt = 3-hydroxy-2-methyl-4-pyronate) (2) react with DL-alpha-dipalmitoylphosphatidylcholine (DPPC) under a 1:1 molar ratio in CDCl3 at 37 degrees C, as shown by the substantial release of ligands (20-50%) from the metal coordination sphere (1H-NMR), by evident changes in the 1H-NMR spectrum of DPPC in the reaction mixture and by the appearance of a 31P-NMR signal due to metal-coordinated DPPC. 31P-NMR spectra reveal that both 1 and 2 also react with DPPC in water, in the presence of 1% Triton X-100 and Tris buffer. Under these conditions, 1 and 2 do not react with ghosts from human erythrocytes. On the contrary, the far less hydrolytically stable complex Al(lact)3 (lact = lactate) appears to be reactive under identical conditions, as shown by 31P-NMR spectra.

Aluminium(III) in experimental cell pathology.

Controversy over the relevance of aluminium to certain human encephalopathies has emphasized the importance of in vivo and in vitro models as tools for shedding light on the biological and molecular aspects of the aluminium toxicity. The search for an experimental model in animals or in cultured cells able to reproduce specific pathological human conditions may prove to be an unattainable aim; nevertheless, in vivo and in vitro models should be actively sought and the pathological changes induced in experimental animals should always be evaluated at the cellular level, just as for changes produced directly in cultured cells. These toxicological aspects are outlined with particular emphasis on the role played by the molecular form of aluminium (metal speciation) in determining the quality and intensity of the metal's biological effects.

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.