-
Journal of Trace Elements in Medicine... Mar 2018Autism spectrum disorder is a neurodevelopmental disorder of unknown aetiology. It is suggested to involve both genetic susceptibility and environmental factors...
Autism spectrum disorder is a neurodevelopmental disorder of unknown aetiology. It is suggested to involve both genetic susceptibility and environmental factors including in the latter environmental toxins. Human exposure to the environmental toxin aluminium has been linked, if tentatively, to autism spectrum disorder. Herein we have used transversely heated graphite furnace atomic absorption spectrometry to measure, for the first time, the aluminium content of brain tissue from donors with a diagnosis of autism. We have also used an aluminium-selective fluor to identify aluminium in brain tissue using fluorescence microscopy. The aluminium content of brain tissue in autism was consistently high. The mean (standard deviation) aluminium content across all 5 individuals for each lobe were 3.82(5.42), 2.30(2.00), 2.79(4.05) and 3.82(5.17) μg/g dry wt. for the occipital, frontal, temporal and parietal lobes respectively. These are some of the highest values for aluminium in human brain tissue yet recorded and one has to question why, for example, the aluminium content of the occipital lobe of a 15year old boy would be 8.74 (11.59) μg/g dry wt.? Aluminium-selective fluorescence microscopy was used to identify aluminium in brain tissue in 10 donors. While aluminium was imaged associated with neurones it appeared to be present intracellularly in microglia-like cells and other inflammatory non-neuronal cells in the meninges, vasculature, grey and white matter. The pre-eminence of intracellular aluminium associated with non-neuronal cells was a standout observation in autism brain tissue and may offer clues as to both the origin of the brain aluminium as well as a putative role in autism spectrum disorder.
Topics: Adolescent; Adult; Aluminum; Autism Spectrum Disorder; Brain; Brain Chemistry; Cell Line; Female; Humans; Male; Middle Aged; Young Adult
PubMed: 29413113
DOI: 10.1016/j.jtemb.2017.11.012 -
Journal of Toxicology and Environmental... 2007
Review
Topics: Aluminum; Aluminum Compounds; Aluminum Hydroxide; Aluminum Oxide; Animals; Environmental Exposure; Humans; Occupational Exposure; Risk Assessment; Tissue Distribution; Toxicity Tests
PubMed: 18085482
DOI: 10.1080/10937400701597766 -
International Journal of Molecular... Sep 2021Chromosome instability (CIN) consists of high rates of structural and numerical chromosome abnormalities and is a well-known hallmark of cancer. Aluminum is added to...
Chromosome instability (CIN) consists of high rates of structural and numerical chromosome abnormalities and is a well-known hallmark of cancer. Aluminum is added to many industrial products of frequent use. Yet, it has no known physiological role and is a suspected human carcinogen. Here, we show that V79 cells, a well-established model for the evaluation of candidate chemical carcinogens in regulatory toxicology, when cultured in presence of aluminum-in the form of aluminum chloride (AlCl) and at concentrations in the range of those measured in human tissues-incorporate the metal in a dose-dependent manner, predominantly accumulating it in the perinuclear region. Intracellular aluminum accumulation rapidly leads to a dose-dependent increase in DNA double strand breaks (DSB), in chromosome numerical abnormalities (aneuploidy) and to proliferation arrest in the G2/M phase of the cell cycle. During mitosis, V79 cells exposed to aluminum assemble abnormal multipolar mitotic spindles and appear to cluster supernumerary centrosomes, possibly explaining why they accumulate chromosome segregation errors and damage. We postulate that chronic aluminum absorption favors CIN in mammalian cells, thus promoting carcinogenesis.
Topics: Aluminum; Aluminum Chloride; Animals; Cell Line; Centromere; Chromosomal Instability; Chromosomes, Mammalian; Cricetulus; DNA Breaks, Double-Stranded; G2 Phase Cell Cycle Checkpoints; M Phase Cell Cycle Checkpoints
PubMed: 34502420
DOI: 10.3390/ijms22179515 -
The National Medical Journal of India 2019Aluminium utensils are ubiquitous in Indian households and other developing countries. Concerns have recently been raised on the pathological effects of aluminium on the... (Review)
Review
Aluminium utensils are ubiquitous in Indian households and other developing countries. Concerns have recently been raised on the pathological effects of aluminium on the human body, due to its leaching from utensils with long-term use, which has been associated with certain clinical conditions such as anaemia, dementia and osteo-malacia. While some studies suggest that cooking in utensils or aluminium foils is safe, others suggest that it may lead to toxic levels of aluminium in the body. However, studies have shown that leaching of aluminium from cooking utensils depends on many factors such as pH, temperature and cooking medium. In healthy controls, 0.01 %-1 % of orally ingested aluminium is absorbed from the gastrointestinal tract and is eliminated by the kidney. Although the metal has a tendency to accumulate in tissues and may result in their dysfunction, the literature suggests that the apprehension is more apt in patients with chronic renal insufficiency. This article offers solutions to mitigate the risk of aluminium toxicity.
Topics: Aluminum; Anemia; Cooking and Eating Utensils; Dementia; Hot Temperature; Humans; India; Intestinal Absorption; Manufacturing Industry; Osteomalacia; Renal Elimination; Time Factors
PubMed: 31823940
DOI: 10.4103/0970-258X.272116 -
Molecules (Basel, Switzerland) Aug 2022The natural element aluminum possesses a number of unique biochemical and biophysical properties that make this highly neurotoxic species deleterious towards the...
The natural element aluminum possesses a number of unique biochemical and biophysical properties that make this highly neurotoxic species deleterious towards the structural integrity, conformation, reactivity and stability of several important biomolecules. These include aluminum's small ionic size and highly electrophilic nature, having the highest charge density of any metallic cation with a Z/r of 18 (ionic charge +3, radius 0.5 nm); inclination to form extremely stable electrostatic bonds with a tendency towards covalency; ability to interact irreversibly and/or significantly slow down the exchange-rates of complex aluminum-biomolecular interactions; extremely dense electropositive charge with one of the highest known affinities for oxygen-donor ligands such as phosphate; presence as the most abundant metal in the Earth's biosphere and general bioavailability in drinking water, food, medicines, consumer products, groundwater and atmospheric dust; and abundance as one of the most commonly encountered intracellular and extracellular metallotoxins. Despite aluminum's prevalence and abundance in the biosphere it is remarkably well-tolerated by all plant and animal species; no organism is known to utilize aluminum metabolically; however, a biological role for aluminum has been assigned in the compaction of chromatin. In this Communication, several examples are given where aluminum has been shown to irreversibly perturb and/or stabilize the natural conformation of biomolecules known to be important in energy metabolism, gene expression, cellular homeostasis and pathological signaling in neurological disease. Several neurodegenerative disorders that include the tauopathies, Alzheimer's disease and multiple prion disorders involve the altered conformation of naturally occurring cellular proteins. Based on the data currently available we speculate that one way aluminum contributes to neurological disease is to induce the misfolding of naturally occurring proteins into altered pathological configurations that contribute to the neurodegenerative disease process.
Topics: Aluminum; Alzheimer Disease; Animals; Neurodegenerative Diseases; Neurotoxicity Syndromes; Protein Conformation; Proteostasis Deficiencies
PubMed: 36014365
DOI: 10.3390/molecules27165123 -
Scientific Reports Feb 2020The knowledge about a potential in vivo uptake and subsequent toxicological effects of aluminum (Al), especially in the nanoparticulate form, is still limited. This...
The knowledge about a potential in vivo uptake and subsequent toxicological effects of aluminum (Al), especially in the nanoparticulate form, is still limited. This paper focuses on a three day oral gavage study with three different Al species in Sprague Dawley rats. The Al amount was investigated in major organs in order to determine the oral bioavailability and distribution. Al-containing nanoparticles (NMs composed of Al and aluminum oxide (AlO)) were administered at three different concentrations and soluble aluminum chloride (AlCl·6HO) was used as a reference control at one concentration. A microwave assisted acid digestion approach followed by inductively coupled plasma mass spectrometry (ICP-MS) analysis was developed to analyse the Al burden of individual organs. Special attention was paid on how the sample matrix affected the calibration procedure. After 3 days exposure, AlCl·6HO treated animals showed high Al levels in liver and intestine, while upon treatment with Al NMs significant amounts of Al were detected only in the latter. In contrast, following AlO NMs treatment, Al was detected in all investigated organs with particular high concentrations in the spleen. A rapid absorption and systemic distribution of all three Al forms tested were found after 3-day oral exposure. The identified differences between Al and AlO NMs point out that both, particle shape and surface composition could be key factors for Al biodistribution and accumulation.
Topics: Administration, Oral; Aluminum; Aluminum Chloride; Aluminum Oxide; Animals; Biological Availability; Humans; Intestines; Liver; Nanostructures; Rats; Rats, Sprague-Dawley; Spleen; Tissue Distribution
PubMed: 32060369
DOI: 10.1038/s41598-020-59710-z -
Journal of Occupational and... May 2014This introduction to the industrial primary aluminum production process presents a short description of the electrolytic reduction technology, the history of aluminum,...
This introduction to the industrial primary aluminum production process presents a short description of the electrolytic reduction technology, the history of aluminum, and the importance of this metal and its production process to modern society. Aluminum's special qualities have enabled advances in technologies coupled with energy and cost savings. Aircraft capabilities have been greatly enhanced, and increases in size and capacity are made possible by advances in aluminum technology. The metal's flexibility for shaping and extruding has led to architectural advances in energy-saving building construction. The high strength-to-weight ratio has meant a substantial reduction in energy consumption for trucks and other vehicles. The aluminum industry is therefore a pivotal one for ecological sustainability and strategic for technological development.
Topics: Aluminum; Aluminum Oxide; History, 19th Century; History, 20th Century; History, 21st Century; Metallurgy; Technology
PubMed: 24806722
DOI: 10.1097/JOM.0000000000000154 -
Environmental Health Perspectives Nov 1994This review discusses recent literature on the chemical and physiological factors that influence the absorption, distribution, and excretion of aluminum in mammals, with... (Review)
Review
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.
Topics: Absorption; Aluminum; Alzheimer Disease; Environmental Exposure; Environmental Pollutants; Humans
PubMed: 9738208
DOI: 10.1289/ehp.94102940 -
Brain Pathology (Zurich, Switzerland) Mar 2016Aluminum is a ubiquitously abundant nonessential element. Aluminum has been associated with neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic... (Review)
Review
Aluminum is a ubiquitously abundant nonessential element. Aluminum has been associated with neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis, and dialysis encephalopathy. Many continue to regard aluminum as controversial although increasing evidence supports the implications of aluminum in the pathogenesis of AD. Aluminum causes the accumulation of tau protein and Aβ protein in the brain of experimental animals. Aluminum induces neuronal apoptosis in vivo and in vitro, either by endoplasmic stress from the unfolded protein response, by mitochondrial dysfunction, or a combination of them. Some, people who are exposed chronically to aluminum, either from through water and/or food, have not shown any AD pathology, apparently because their gastrointestinal barrier is more effective. This article is written keeping in mind mechanisms of action of aluminum neurotoxicity with respect to AD.
Topics: Aluminum; Alzheimer Disease; Animals; Hippocampus; Humans
PubMed: 26494454
DOI: 10.1111/bpa.12333 -
Medycyna Pracy Jan 2020This work features a review of literature discussing the health effects of environmental and occupational exposure to aluminum (Al) and its compounds. The sources of... (Review)
Review
This work features a review of literature discussing the health effects of environmental and occupational exposure to aluminum (Al) and its compounds. The sources of exposure, absorption routes and metabolism are discussed in detail. The role of Al and its compounds in the etiology of some diseases, related to both environmental exposure and exposure in the work environment, is also presented. Aluminum toxicity most often affects the central nervous system, the skeletal system, the hematopoietic system, the urinary tract and the respiratory system. An increased effect of active forms of oxygen can stimulate the formation of amyloid deposits. The clinical image of aluminum smelters was dominated by ataxia, memory impairment, impaired abstract thinking and depressive states. Aluminum compounds have a detrimental effect not only on the psychic but also motor skills. Med Pr. 2020;71(1):79-88.
Topics: Aluminum; Humans; Occupational Exposure
PubMed: 31688841
DOI: 10.13075/mp.5893.00887