Aluminium blunts the proliferative response, and increases apoptosis of cultured human cells: putative relationship to alzheimer’s disease

Abstract

Abstract:Aluminium (Al) has been investigated as a neurotoxic substance. Al ranks among the potential environmental risk factors for Alzheimer's disease (AD). Epidemiological studies tested the relationship between Al in drinking water and AD, showing a significant correlation between elevated levels of monomeric Al in water and AD, although data to date remain inconclusive with respect to total Al. The aim of this study was to test whether or not Al exacerbates cellular toxicity mediated by the amyloid β (Aβ) peptide. We evaluated the role of Al in modulating programmed cell death (apoptosis) in human cell cultures. We used the osteosarcoma cell line monolayer (SaOs-2) to demonstrate that treatment of SaOs-2 cultures with the Aβ peptide mid-fragment (25 to 35) at nano M, followed by co-incubation with physiological concentrations of aluminium chloride, which release monomeric Al in solution, led to marked expression of caspase 3, but not caspase 9, key markers of the apoptotic process. The same experimental conditions were shown to blunt significantly the proliferative response of normal human peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA) stimulation. Our observations support the hypothesis that Al significantly impairs certain cellular immune responses, and confirm that Al-mediated cell toxicity may play an important role in AD.

Impacts of alum residues from Morton Jaffray Water Works on water quality and fish, Harare, Zimbabwe

“…No study has been carried out in the country concerning the residues from Morton Jaffray and their effect on fish as well as quality of the receiving water bodies. It has been shown elsewhere, however, that Al accumulates in sediments and water and that Al bioaccumulates in fish and its toxic effects in fish have been reported in literature (Abdullah et al, 1995;Giller and Malmquist, 1998;PBC, 1998;Coetzee et al, 2002;Sharma, 2003;Kegley et al, 2009) as well as in humans (Prolo et al, 2007).…”

“…Canadian Water Quality Guidelines for Protection of Aquatic Organisms (CEQG, 2003) use 100 µg/l Al for freshwater whereas the United States Environmental Protection Agency (EPA) guideline for continuous exposure to Al by aquatic life is 87 µg/l (EPA-AU, 2006). Aluminium toxicity has also been shown in humans where it causes neurological disorders such as dialysis encephalopathy and onset of Alzheimer's disease (Prolo et al, 2007). This is particularly so for patients on haemodialysis being administered with oral aluminium hydroxide as a phosphate binder (Ghori and Yaqub, 1999).…”

“…Aluminium in drinking water has been linked to occurrences of Alzheimer disease and other neurological disorders (Ghori and Yaqub, 1999;Prolo et al, 2007). Nhapi (2007) recommended increased raw water abstractions from Lake Manyame.…”

“…Aluminium exists as a trivalent cation, Al 3+ , and because also of its small ionic radius (0.51), it is too reactive to be found free in nature . Total Al comprises suspended Al, colloidal Al and monomeric Al of which the first two form the particulate fraction of Al (Prolo et al, 2007). Monomeric Al occurs as the non-labile or water-insoluble (organic) Al that is associated with dissolved organic carbon and as the labile or water soluble inorganic Al (Prolo et al, 2007).…”

Health risk implications from simultaneous exposure to multiple environmental contaminants

“…Premature infants have been found to be the most sensitive to Al exposure (Hellström et al, 2008;Driscoll et al, 1997). Aluminium is exponentially accumulated in the body with ageing and can trigger excess apoptosis (cell death) (Ganrot, 1986) which impairs certain cellular immune responses (Prolo et al, 2007). These impacts are of special concern in South Africa, where the elderly and HIV infected persons already suffer from compromised immune systems making them even more vulnerable to other serious infections (Hellström et al, 2008).…”