Dietary Egg White Hydrolysate Prevents Male Reproductive Dysfunction after Long-Term Exposure to Aluminum in Rats.

Aluminum (Al) is a non-essential metal omnipresent in human life and is considered an environmental toxicant. Al increases reactive oxygen production and triggers immune responses, contributing to chronic systemic inflammation development. Here, we have tested whether an egg white hydrolysate (EWH) with potential bioactive properties can protect against changes in reproductive function in rats exposed to long-term Al dietary levels at high and low doses. Male Wistar rats received orally: low aluminum level group-AlCl3 at 8.3 mg/kg b.w. for 60 days with or without EWH (1 g/kg/day); high aluminum level group-AlCl3 at 100 mg/kg b.w. for 42 days with or without EWH (1 g/kg/day). The co-administration of EWH prevented the increased Al deposition surrounding the germinative cells, reducing inflammation and oxidative stress in the reproductive organs. Furthermore, the daily supplementation with EWH maintained sperm production and sperm quality similar to those found in control animals, even after Al exposure at a high dietary contamination level. Altogether, our results suggest that EWH could be used as a protective agent against impairment in the reproductive system produced after long-term exposure to Al at low or high human dietary levels.

Aluminum and Amyloid-ß in Familial Alzheimer's Disease.

Genetic predispositions associated with metabolism of the amyloid-ß protein precursor underlie familial Alzheimer's disease; a form of dementia characterized by early disease onset and elevated levels of cortical amyloid-ß. Human exposure to aluminum is linked to the etiology of Alzheimer's disease and recent research measured a high content of aluminum in brain tissue in familial Alzheimer's disease. To elaborate upon this finding, we have obtained brain tissues from a Colombian cohort of donors with familial Alzheimer's disease. We have used established methods to measure the aluminum content of these tissues and we have compared the data with a recently measured dataset for control brain tissues. We report significantly higher levels of aluminum in brain tissues in donors with familial Alzheimer's disease than in control tissues from donors without neurological impairment or neurodegeneration. We have used aluminum-specific fluorescence microscopy along with complementary imaging for amyloid-ß to demonstrate a very high degree of co-localization of these two risk factors in brain tissue in familial Alzheimer's disease. Aluminum and amyloid-ß were co-located in senile plaques as well as vasculature, the latter resembling cerebral amyloid angiopathy. Aluminum was also found separately from amyloid-ß in intracellular compartments including glia and neuronal axons. The research has identified an arguably unique association between high brain aluminum content and amyloid-ß and allows postulation that genetic predispositions defining familial Alzheimer's disease underlie this relationship.

Aluminum affects neural phenotype determination of embryonic neural progenitor cells.

Aluminum (Al) is a neurotoxin and is associated with the etiology of neurodegenerative diseases, such as Alzheimer's disease (AD). The Al-free ion (Al3+) is the biologically reactive and toxic form. However, the underlying mechanisms of Al toxicity in the brain remain unclear. Here, we evaluated the effects of Al3+ (in the chloride form-AlCl3) at different concentrations (0.1-100 µM) on the morphology, proliferation, apoptosis, migration and differentiation of neural progenitor cells (NPCs) isolated from embryonic telencephalons, cultured as neurospheres. Our results reveal that Al3+ at 100 µM reduced the number and diameter of neurospheres. Cell cycle analysis showed that Al3+ had a decisive function in proliferation inhibition of NPCs during neural differentiation and induced apoptosis on neurospheres. In addition, 1 µM Al3+ resulted in deleterious effects on neural phenotype determination. Flow cytometry and immunocytochemistry analysis showed that Al3+ promoted a decrease in immature neuronal marker ß3-tubulin expression and an increase in co-expression of the NPC marker nestin and glial fibrillary acidic protein. Thus, our findings indicate that Al3+ caused cellular damage and reduced proliferation and migration, resulting in global inhibition of NPC differentiation and neurogenesis.

Egg White Hydrolysate as a functional food ingredient to prevent cognitive dysfunction in rats following long-term exposure to aluminum.

Aluminum (Al), which is omnipresent in human life, is a potent neurotoxin. Here, we have tested the potential for Egg White Hydrolysate (EWH) to protect against changes in cognitive function in rats exposed to both high and low levels of Al. Indeed, EWH has been previously shown to improve the negative effects induced by chronic exposure to heavy metals. Male Wistar rats received orally: Group 1) Low aluminum level (AlCl3 at a dose of 8.3 mg/kg b.w. during 60 days) with or without EWH treatment (1 g/kg/day); Group 2) High aluminum level (AlCl3 at a dose of 100 mg/kg b.w. during 42 days) with or without EWH treatment (1 g/kg/day). After 60 or 42 days of exposure, rats exposed to Al and EWH did not show memory or cognitive dysfunction as was observed in Al-treated animals. Indeed, co-treatment with EWH prevented catalepsy, hippocampal oxidative stress, cholinergic dysfunction and increased number of activated microglia and COX-2-positive cells induced by Al exposure. Altogether, since hippocampal inflammation and oxidative damage were partially prevented by EWH, our results suggest that it could be used as a protective agent against the detrimental effects of long term exposure to Al.

Aluminum exposure at human dietary levels promotes vascular dysfunction and increases blood pressure in rats: A concerted action of NAD(P)H oxidase and COX-2.

Aluminum (Al) is a non-essential metal and a significant environmental contaminant and is associated with a number of human diseases including cardiovascular disease. We investigated the effects of Al exposure at doses similar to human dietary levels on the cardiovascular system over a 60day period. Wistar male rats were divided into two major groups and received orally: 1) Low aluminum level - rats were subdivided and treated for 60days as follows: a) Untreated - ultrapure water; b) AlCl3 at a dose of 8.3mg/kg bw for 60days, representing human Al exposure by diet; and 2) High aluminum level - rats were subdivided and treated for 42days as follows: C) Untreated - ultrapure water; d) AlCl3 at 100mg/kg bw for 42days, representing a high level of human exposure to Al. Effects on systolic blood pressure (SBP) and vascular function of aortic and mesenteric resistance arteries (MRA) were studied. Endothelium and smooth muscle integrity were evaluated by concentration-response curves to acetylcholine (ACh) and sodium nitroprusside. Vasoconstrictor responses to phenylephrine (Phe) in the presence and absence of endothelium and in the presence of the NOS inhibitor L-NAME, the potassium channels blocker TEA, the NAD(P)H oxidase inhibitor apocynin, superoxide dismutase (SOD), the non-selective COX inhibitor indomethacin and the selective COX-2 inhibitor NS 398 were analyzed. Vascular reactive oxygen species (ROS), lipid peroxidation and total antioxidant capacity, were measured. The mRNA expressions of eNOS, NAD(P)H oxidase 1 and 2, SOD1, COX-2 and thromboxane A2 receptor (TXA-2 R) were also investigated. Al exposure at human dietary levels impaired the cardiovascular system and these effects were almost the same as Al exposure at much higher levels. Al increased SBP, decreased ACh-induced relaxation, increased response to Phe, decreased endothelial modulation of vasoconstrictor responses, the bioavailability of nitric oxide (NO), the involvement of potassium channels on vascular responses, as well as increased ROS production from NAD(P)H oxidase and contractile prostanoids mainly from COX-2 in both aorta and mesenteric arteries. Al exposure increased vascular ROS production and lipid peroxidation as well as altered the antioxidant status in aorta and MRA. Al decreased vascular eNOS and SOD1 mRNA levels and increased the NAD(P)H oxidase 1, COX-2 and TXA-2 R mRNA levels. Our results point to an excess of ROS mainly from NAD(P)H oxidase after Al exposure and the increased vascular prostanoids from COX-2 acting in concert to decrease NO bioavailability, thus inducing vascular dysfunction and increasing blood pressure. Therefore, 60-day chronic exposure to Al, which reflects common human dietary Al intake, appears to pose a risk for the cardiovascular system.

Aluminium-induced phospholipid signal transduction pathway in Coffea arabica suspension cells and its amelioration by silicic acid.

Coffee (Coffea arabica L.) is of economic importance worldwide. Its growth in organic-rich acidic soils is influenced by aluminium such that coffee yield may be impaired. Herein we have used the Al-sensitive C. arabica suspension cell line L2 to analyse the effect of two different Al species on the phosphoinositide signal transduction pathway. Our results have shown that the association of Al with coffee cells was affected by the pH and the form of Al in media. More Al was associated with cells at pH 4.3 than 5.8, whereas when Al was present as hydroxyaluminosilicates (HAS) the association was halved at pH 4.3 and unchanged at pH 5.8. Two signal transduction elements were also evaluated; phospholipase C (PLC) activity and phosphatidic acid (PA) formation. PLC was inhibited ( approximately 50%) when cells were incubated for 2 h in the presence of either AlCl(3) or Al in the form of HAS. PA formation was tested as a short-term response to Al. By way of contrast to what was found for PLC, incubation of cells for 15 min in the presence of AlCl(3) decreased the formation of PA whereas the same concentration of Al as HAS produced no effect upon its formation. These results suggest that Al is capable to exert its effects upon signal transduction as Al((aq))(3+) acting upon a mechanism linked to the phosphoinositide signal transduction pathway.