Memory Deficit in Mice Administered Aluminum–maltolate Complex

Recently, aluminum (Al) has been identified as one of the environmental factors responsible for cause certain nerve degeneration diseases, particularly, Alzheimer’s disease (AD). However, the relationship between Al and AD is controversial. We previously examined whether Al induced neurotoxin in the brain of mice when aluminum–maltolate complex (ALM) was administered daily for 120 days. Our results revealed that Al accumulated in the brain induced oxidative stress, and the nerve degeneration was detected in the brain of the ALM-treated group. On the basis of these results, we have tried to examine whether the incorporated Al affects memory in mice with regard to an indicator of spatial memory deficits depending on the chemical forms of Al, namely, as an ion (AlCl₃) and in the form of a complex (ALM). We administered saline, AlCl₃, and ALM at a concentration of 40 μmol Al/kg body weight to mice by daily ip injections for 60 days. We assessed spatial memory by a water maze task and determined the Al levels in the brain of the mice by the neutron activation analysis method. Spatial memory deficit as an indicator of the swimming time was related to Al accumulation in the brain of mice; the chemical form of the Al compound was important in order to exhibit the memory deficit in mice; the uptake of Al is higher in mice when it is administered in a complex form than in an ionic form.     

How Bad Is Aluminum Exposure to Reproductive Parameters in Rats?

The objective of this study was to evaluate influence of dietary palygorskite (Pal) supplementation on growth performance, mineral accumulations in the tissues (livers, kidneys, and muscles), antioxidant capacities, and meat quality of broilers fed lead (Pb)-contaminated diet. One-hundred forty-four male broiler chicks were randomly divided into three treatment groups, receiving a corn-soybean meal basal diet (the control group), the basal diet contaminated with 10 mg/kg Pb (the Pb group), and the basal diet with 10-g/kg Pal supplementation and 10-mg/kg Pb contamination (the Pal/Pb group) from 1 to 42 days of age, respectively. Treatments did not affect growth performance of broilers in the 42-day study (P > 0.05). Compared with the control group, Pb contamination increased Pb accumulation in the livers, kidneys, and muscles (P < 0.05); elevated malondialdehyde accumulation in the livers, kidneys, and breast muscles; glutathione peroxidase activity in the livers and superoxide dismutase activity in the kidneys (P < 0.05); exacerbated drip loss in the pectoralis muscles (P < 0.05); and reduced glutathione peroxidase activity in the pectoralis muscles (P < 0.05) of broilers at 42 days of age. The values of these parameters were reversed in the Pal/Pb group to levels comparable with those in the control group (P < 0.05). Additionally, Pal supplementation reduced redness value in the pectoralis muscles (P < 0.05), and decreased Cu concentration in the pectoralis muscles and livers at 42 days of age as well as its accumulation in the kidneys at both 21 and 42 days of age compared with the other two groups (P < 0.05). The results suggested that dietary Pal supplementation would decrease Pb residue in the tissues, alleviate oxidative stress, and affect meat quality of broilers exposed to Pb.     

Urinary Profile of 6β-Hydroxycortisol in Workers Exposed to Aluminum

The aim of the present study was to evaluate whether aluminum exposure may cause alterations of cytochrome P ₄₅₀3A4 by measuring the urinary excretion of 6β-hydroxycortisol as biomarker. There is a positive correlation between urinary 6β-hydroxycortisol and aluminum excretion (p < 0.05). The correlations between occupational duration, smoking habits, and age were also evaluated. The increased excretion of the biomarker suggests that this element may induce formation of cytochrome P ₄₅₀ in exposed individuals.     

Aluminum accumulation and associated effects on 15NO3 − influx in roots of two soybean genotypes differing in Al tolerance

A study was conducted to examine aluminum (Al) exclusion by roots of two differentially tolerant soybean (Glycine max L. Merr.) lines, Pl-416937 (Al-tolerant) and Essex (Al-sensitive). Following exposure to 80μM Al for up to 2 h, roots were rinsed with a 10 mM potassium citrate solution and rapidly dissected to allow estimation of intracellular Al accumulation in morphologically distinct root regions. Using 10 min exposures to 300μM ¹⁵NO₃ ⁻ and dissection, accompanying effects on NO₃ ⁻ uptake were measured. With Al exposures of 20 min or 2 h, there was greater Al accumulation in all root regions of Essex than in those of Pl-416937. The genotypic difference in Al accumulation was particularly apparent at the root apex, both in the tip and in the adjacent root cap and mucilage. Exposure of roots to Al inhibited the uptake of ¹⁵NO₃ ⁻ to a similar extent in all root regions. The results are consistent with Al exclusion from cells in the root apical region being an important mechanism of Al tolerance.     

Aluminum effects on marine phytoplankton: implications for a revised Iron Hypothesis (Iron–Aluminum Hypothesis)

In contrast to substantial studies and established knowledge of aluminum (Al) effects (mainly toxicity) on freshwater organisms and terrestrial plants, and even on human health, only a few studies of Al effects on marine organisms have been reported, and our understanding of the role of Al in marine biogeochemistry is limited. In this paper, we review the results of both field and laboratory experiments on the effects of Al on marine organisms, including Al toxicity to marine phytoplankton and the beneficial effects of Al on marine phytoplankton growth, and we discuss possible links of Al to the biological pump and the global carbon cycle. We propose a revised Iron (Fe) Hypothesis, i.e., the Fe–Al Hypothesis that introduces the idea that Al as well as Fe play an important role in the glacial-interglacial change in atmospheric CO₂ concentrations and climate change. We propose that Al could not only facilitate Fe utilization, dissolved organic phosphorus utilization and nitrogen fixation by marine phytoplankton, enhancing phytoplankton biomass and carbon fixation in the upper oceans, but also reduce the decomposition and decay of biogenic matter. As a result, Al allows potentially more carbon to be exported and sequestered in the ocean depths through the biological pump. We also propose that Al binds to superoxide to form an Al-superoxide complex, which could catalyze the reduction of Fe(III) to Fe(II) and thus facilitate Fe utilization by marine phytoplankton and other microbes. Further ocean fertilization experiments with Fe and Al are suggested, to clarify the role of Al in the stimulation of phytoplankton growth and carbon sequestration in the ocean depths.     

Do Cadmium, Lead, and Aluminum in Drinking Water Increase the Risk of Hip Fractures? A NOREPOS Study

The aim of this study was to investigate relations between cadmium, lead, and aluminum in municipality drinking water and the incidence of hip fractures in the Norwegian population. A trace metals survey in 566 waterworks was linked geographically to hip fractures from hospitals throughout the country (1994–2000). In all those supplied from these waterworks, 5,438 men and 13,629 women aged 50–85 years suffered a hip fracture. Poisson regression models were fitted, adjusting for age, region of residence, urbanization, and type of water source as well as other possibly bone-related water quality factors. Effect modification by background variables and interactions between water quality factors were examined (correcting for false discovery rate). Men exposed to a relatively high concentration of cadmium (IRR?=?1.10; 95 % CI 1.01, 1.20) had an increased risk of fracture. The association between relatively high lead and hip fracture risk was significant in the oldest age group (66–85 years) for both men (IRR?=?1.11; 95 % CI 1.02, 1.21) and women (IRR?=?1.10; 95 % CI 1.04, 1.16). Effect modification by degree of urbanization on hip fracture risk in men was also found for all three metals: cadmium, lead, and aluminum. In summary, a relatively high concentration of cadmium, lead, and aluminum measured in drinking water increased the risk of hip fractures, but the associations depended on gender, age, and urbanization degree. This study could help in elucidating the complex effects on bone health by risk factors found in the environment.     

Aluminum Trichloride Inhibited Osteoblastic Proliferation and Downregulated the Wnt/β-Catenin Pathway

Aluminum (Al) exposure inhibits bone formation. Osteoblastic proliferation promotes bone formation. Therefore, we inferred that Al may inhibit bone formation by the inhibition of osteoblastic proliferation. However, the effects and molecular mechanisms of Al on osteoblastic proliferation are still under investigation. Osteoblastic proliferation can be regulated by Wnt/β-catenin signaling pathway. To investigate the effects of Al on osteoblastic proliferation and whether Wnt/β-catenin signaling pathway is involved in it, osteoblasts from neonatal rats were cultured and exposed to 0, 0.4 mM (1/20 IC₅₀), 0.8 mM (1/10 IC₅₀), and 1.6 mM (1/5 IC₅₀) of aluminum trichloride (AlCl₃) for 24 h, respectively. The osteoblastic proliferation rates; Wnt3a, lipoprotein receptor-related protein 5 (LRP-5), T cell factor 1 (TCF-1), cyclin D1, and c-Myc messenger RNA (mRNA) expressions; and p-glycogen synthase kinase 3β (GSK3β), GSK3β, and β-catenin protein expressions indicated that AlCl₃ inhibited osteoblastic proliferation and downregulated Wnt/β-catenin signaling pathway. In addition, the AlCl₃ concentration was negatively correlated with osteoblastic proliferation rates and the mRNA expressions of Wnt3a, c-Myc, and cyclin D1, while the osteoblastic proliferation rates were positively correlated with mRNA expressions of Wnt3a, c-Myc, and cyclin D1. Taken together, these findings indicated that AlCl₃ inhibits osteoblastic proliferation may be associated with the inactivation of Wnt/β-catenin signaling pathway.     

Polymer–Magnesium Aluminum Silicate Composite Dispersions for Improved Physical Stability of Acetaminophen Suspensions

The aims of this study were to characterize the morphology and size of flocculates and the zeta potential and rheological properties of polymer–magnesium aluminum silicate (MAS) composite dispersions and to investigate the physical properties of acetaminophen (ACT) suspensions prepared using the composite dispersions as a flocculating/suspending agent. The polymers used were sodium alginate (SA), sodium carboxymethylcellulose (SCMC), and methylcellulose (MC). The results showed that SA, SCMC, and MC could induce flocculation of MAS by a polymer-bridging mechanism, leading to the changes in the zeta potential of MAS and the flow properties of the polymer dispersions. The microscopic morphology and size of the flocculates was dependent on the molecular structure of the polymer, especially ether groups on the polymer side chain. The residual MAS from the flocculation could create a three-dimensional structure in the SA–MAS and SCMC–MAS dispersions, which brought about not only an enhancement of viscosity and thixotropic properties but also an improvement in the ACT flocculating efficiency of polymers. The use of polymer–MAS dispersions provided a higher degree of flocculation and a lower redispersibility value of ACT suspensions compared with the pure polymer dispersions. This led to a low tendency for caking of the suspensions. The SCMC–MAS dispersions provided the highest ACT flocculating efficiency, whereas the lowest ACT flocculating efficiency was found in the MC–MAS dispersions. Moreover, the added MAS did not affect ACT dissolution from the suspensions in an acidic medium. These findings suggest that the polymer–MAS dispersions show good potential for use as a flocculating/suspending agent for improving the rheological properties and physical stability of the suspensions.     

Protective Role of Melatonin on Oxidative Stress Status and RNA Expression in Cerebral Cortex and Cerebellum of AβPP Transgenic Mice After Chronic Exposure to Aluminum

Aluminum (Al) has been associated with pro-oxidant effects, as well as with various serious neurodegenerative diseases such as Alzheimer’s disease (AD). On the other hand, melatonin (Mel) is a known antioxidant, which can directly act as free radical scavenger, or indirectly by inducing the expression of some genes linked to the antioxidant defense. In this study, 5-month-old AßPP female transgenic (Tg2576) (Tg) and wild-type mice were fed with Al lactate supplemented in the diet (1 mg Al/g diet). Concurrently, animals received oral Mel (10 mg/kg) until the end of the study at 11 months of age. Four treatment groups were included for both Tg and wild-type mice: control, Al only, Mel only, and Al + Mel. At the end of the treatment period, cortex and cerebellum were removed and processed to examine the following oxidative stress markers: reduced glutathione, oxidized glutathione, cytosolic Cu–Zn superoxide dismutase (SOD1), glutathione reductase (GR), glutathione peroxidase, catalase (CAT), and thiobarbituric acid reactive substances. Moreover, the gene expression of SOD1, GR, and CAT was evaluated by real-time RT-PCR. The biochemical changes observed in cortex and cerebellum suggest that Al acted as a pro-oxidant agent. Melatonin exerted an antioxidant action by increasing the mRNA levels of the enzymes SOD1, CAT, and GR evaluated in presence of Al and Mel, independently on the animal model.     

Preparation and Characterization of Nicotine–Magnesium Aluminum Silicate Complex-Loaded Sodium Alginate Matrix Tablets for Buccal Delivery

Nicotine (NCT) buccal tablets consisting of sodium alginate (SA) and nicotine–magnesium aluminum silicate (NCT–MAS) complexes acting as drug carriers were prepared using the direct compression method. The effects of the preparation pH levels of the NCT–MAS complexes and the complex/SA ratios on NCT release, permeation across mucosa, and mucoadhesive properties of the tablets were investigated. The NCT–MAS complex-loaded SA tablets had good physical properties and zero-order release kinetics of NCT, which indicate a swelling/erosion-controlled release mechanism. Measurement of unidirectional NCT release and permeation across porcine esophageal mucosa using a modified USP dissolution apparatus 2 showed that NCT delivery was controlled by the swollen gel matrix of the tablets. This matrix, which controlled drug diffusion, resulted from the molecular interactions of SA and MAS. Tablets containing the NCT–MAS complexes prepared at pH 9 showed remarkably higher NCT permeation rates than those containing the complexes prepared at acidic and neutral pH levels. Larger amounts of SA in the tablets decreased NCT release and permeation rates. Additionally, the presence of SA could enhance the mucoadhesive properties of the tablets. These findings suggest that SA plays the important role not only in controlling release and permeation of NCT but also for enhancing the mucoadhesive properties of the NCT–MAS complex-loaded SA tablets, and these tablets demonstrate a promising buccal delivery system for NCT.     

Influence of pH Modifiers and HPMC Viscosity Grades on Nicotine–Magnesium Aluminum Silicate Complex-Loaded Buccal Matrix Tablets

Hydroxypropyl methylcellulose (HPMC) tablets containing nicotine-magnesium aluminum silicate (NCT-MAS) complex particles and pH modifiers, namely, sodium chloride, citric acid, and magnesium hydroxide, were prepared using the direct compression method. The effects of HPMC viscosity grades and pH modifiers on NCT release and permeation of the matrix tablets were examined. The results showed that the higher the viscosity grade of HPMC that was used in the tablets, the lower was the unidirectional NCT release rate found. The unidirectional NCT permeation was not affected by the viscosity grade of HPMC because the NCT diffusion through the mucosal membrane was the rate-limiting step of the permeation. Incorporation of magnesium hydroxide could retard NCT release, whereas the enhancement of unidirectional NCT release was found in the tablets containing citric acid. Citric acid could inhibit NCT permeation due to the formation of protonated NCT in the swollen tablets at an acidic pH. Conversely, the NCT permeation rate increased with the use of magnesium hydroxide as a result of the neutral NCT that formed at a basic microenvironmental pH. The swollen HPMC tablets, with or without pH modifiers, gave sufficient adhesion to the mucosal membrane. Furthermore, the addition of magnesium hydroxide to the matrix tablets was the major factor in controlling buccal delivery of NCT. This study suggests that the NCT-MAS complex-loaded HPMC tablets, which contained magnesium hydroxide, are potential buccal delivery systems of NCT.     

Aluminum, copper, iron and zinc differentially alter amyloid-Aβ(1-42) aggregation and toxicity

Amyloid-β(1-42) (Aβ) is believed to play a crucial role in the ethiopathogenesis of Alzheimer's Disease (AD). In particular, its interactions with biologically relevant metal ions may lead to the formation of highly neurotoxic complexes. Here we describe the species that are formed upon reacting Aβ with several biometals, namely copper, zinc, iron, and with non-physiological aluminum to assess whether different metal ions are able to differently drive Aβ aggregation. The nature of the resulting Aβ-metal complexes and of the respective aggregates was ascertained through a number of biophysical techniques, including electrospray ionization mass spectrometry, dynamic light scattering, fluorescence, transmission electron microscopy and by the use of conformation-sensitive antibodies (OC, αAPF). Metal binding to Aβ is shown to confer highly different chemical properties to the resulting complexes; accordingly, their overall aggregation behaviour was deeply modified. Both aluminum(III) and iron(III) ions were found to induce peculiar aggregation properties, ultimately leading to the formation of annular protofibrils and of fibrillar oligomers. Notably, only Aβ-aluminum was characterized by the presence of a relevant percentage of aggregates with a mean radius slightly smaller than 30 nm. In contrast, both zinc(II) and copper(II) ions completely prevented the formation of soluble fibrillary aggregates. The biological effects of the various Aβ-metal complexes were studied in neuroblastoma cell cultures: Aβ-aluminum turned out to be the only species capable of triggering amyloid precursor and tau181 protein overproduction. Our results point out that Al can effectively interact with Aβ, forming "structured" aggregates with peculiar biophysical properties which are associated with a high neurotoxicity.     

Does Help in Decision-Making in Biology Help in Decision-Making in Human Sciences and Conversely?

A link between biological and human sciences may be established, under the condition that we should admit the existence of reciprocal influences between them. The model for the regulation of agonistic antagonistic couples (MRAAC) is built from the study of biological systems and gives rise to specific types of control. This model can be helpful in decision processes in some human sciences such as management, economical and political strategies. The reason for such an opportunity lies in the fact that MRAAC is a general and phenomenological model able to incorporate the whole of the agonistic antagonistic systems. This type of regulation might be related to the concept of the viability of a system (yet also valid for human science systems) and to a functional and structural pattern which is the basis for agonistic antagonistic networks.     

Calcium signaling in pancreatic β-cells in health and in Type 2 diabetes

Changes in cytosolic free Ca²⁺ concentration ([Ca²⁺]_c) play a crucial role in the control of insulin secretion from the electrically excitable pancreatic β-cell. Secretion is controlled by the finely tuned balance between Ca²⁺ influx (mainly through voltage-dependent Ca²⁺ channels, but also through voltage-independent Ca²⁺ channels like store-operated channels) and efflux pathways. Changes in [Ca²⁺]_c directly affect [Ca²⁺] in various organelles including the endoplasmic reticulum (ER), mitochondria, the Golgi apparatus, secretory granules and lysosomes, as imaged using recombinant targeted probes. Because most of these organelles have specific Ca²⁺ influx and efflux pathways, they mutually influence free [Ca²⁺] in the others. In this article, we review the mechanisms of control of [Ca²⁺] in various compartments and particularly the cytosol, the endoplasmic reticulum ([Ca²⁺]_ER), acidic stores and mitochondrial matrix ([Ca²⁺]_mito), focusing chiefly on the most important physiological stimulus of β-cells, glucose. We also briefly review some alterations of β-cell Ca²⁺ homeostasis in Type 2 diabetes.     

Sex-associated difference in estrogen receptor β expression in N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric cancers in rats

Epidemiologic studies indicate that the incidence of gastric cancer is higher in males than in females. Although the mechanisms mediating this difference are unclear, a role for estrogens has been proposed. We used Western blotting to evaluate the role of estrogen receptor (ER) subtypes ERα and ERβ and proliferating cell nuclear antigen (PCNA) in N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis in Wistar rats; ERα and ERβ mRNA levels also were analyzed by quantitative real-time RT-PCR analysis. The incidence of gastric cancer was significantly higher in male than female rats. In both sexes, ERα expression was similar in MNNG-treated cancerous and noncancerous tissues and normal gastric tissue. However, ERβ expression in MNNG-treated cancerous and noncancerous tissues was significantly lower in male rats and higher in female rats than that in normal gastric tissue; MNNG-induced cancerous tissue showed the highest ERβ expression. PCNA expression in MNNG-treated cancerous tissues was higher than that in noncancerous tissues, and was higher in male rats than female rats. Western blotting results were consistent with the mRNA changes determined by quantitative real-time RT-PCR. The present study provides evidence of a sex-associated difference in ERβ and PCNA expression in MNNG-induced gastric cancers in Wistar rats.