Alzheimer’s Disease and Metal Contamination: Aspects on Genotoxicity

Alzheimer's Disease Pathogenesis-Core Concepts, Shifting Paradigms and Therapeutic Targets 404 demonstrated that brain Al content increases with age and that Al generates reactive oxygen species (ROS) that activates signaling pathways which leads to degeneration of neuronal cells.Together with ROS or alone, Al is biochemically attracted to the DNA reveling its genotoxic and mutagenic potential.Furthermore, high level of Al has been found in brain lesions, such as plaques and tangles, in patients with AD.Several studies demonstrated that among others, Al appears to be the most efficient cation in promoting A aggregation, increasing dramatically cellular neurotoxicity.According to the "amyloid cascade hypothesis", accumulation of A in the brain is the primary event driving AD pathogenesis, increasing the evidences by which Al is involved in AD.Iron is an essential trace element used by almost all living organisms, being often incorporated into the heme complex, which mediate redox reactions.Disturbances of brain iron homeostasis have been linked to acute neuronal injury.Moreover, iron is toxic to neural tissue, leading to neurodegenerative disorders.Organic iron (Fe) may increase the genotoxic effects of other compounds when they are combined.Together with aluminum sulfate, at nanomolar concentrations, iron trigger the release of reactive oxygen species (ROS).In high levels, iron can be mutagenic and genotoxic.In AD, iron is an important cause of oxidative stress because of its overaccumulation in the brain and colocalizes with AD lesions, senile plaques and neurofibrillary tangles.Recent studies also show that homeostasis of essential metals such as copper, iron, selenium and zinc may be altered in the brain of subjects with Alzheimer's disease.It is demonstrated that the plasma concentrations of manganese and total mercury were significantly higher in subjects with AD than in controls, however the concentrations of vanadium, manganese, rubidium, antimony, cesium and lead were significantly lower among subjects with AD cerebrospinal fluid.The influence of metal ions such as Fe, Cu, and Zn in stimulating A aggregation have been widely studied where they appears to vary depending on tissue pH.It should be noticed that, although there is co-localization of metal ions in the pathological markers of AD, this does not indicate a causative role for these elements in the pathogenesis of the disease.Independently of metals being a primary cause or consequence of the disease mechanism, a change in a single metal ion can cause a significant imbalance on homeostasis in elemental levels in the body (serum, CSF and brain) leading to as a sort of "domino effect".It is clear the need to understand the fundamental biochemical mechanisms linking brain biometal metabolism, environmental metal exposure, genotoxicity and AD pathophysiology.In this review, we discuss the role of metals in Alzheimer disease and its involvement in genotoxicity. Source of metal exposureMetals have been used throughout human history to make several utensils, machines, jewelry, and so on, where many of then were obtained through mining and smelting, activities that increases their distribution throughout the environment.Furthermore, the use of metals in industry, medicine, agriculture have been increased over the years, which increase the exposure, not only for those workers involved directly in working with metals but also consumers of the products and the general public through environmental contamination (Ferrer, 2003;Ansari et al., 2004). www.intechopen.comAlzheimer's Disease and Metal Contamination: Aspects on Genotoxicity 405 Metals are among the oldest toxic agents known by humans.Its history starts prior to 2000 BC when it became available as a byproduct of silver smelting.The early Greeks and Romans documented both the toxic as well as the potential healing effects of metals.Theophrastus of Erebus (370-287 BC) and Pliny the Elder (23-79 AD) described the pernicious effects of arsenic and mercury on miners and smelters (Hollenberg, 2010).In an industrialized world, there are thousands of types of metals in use, and humans are exposed to them at work, or as a result of contamination of food, water and environment.There is abundant evidence indicating an increase of neurodegenerative disorders like AD in industrialized countries (Veldman et al., 1998;Butterworth, 2010).The chronic exposure to metals from several years together with the advance of medical tools may explain why the diagnosis of AD and so its epidemic starts around 1980.Aluminum is the most widely distributed metal in the environment and is extensively used in a wide variety of products: cans, foils and kitchen utensils, as well as parts of airplanes, rockets and other items that require a strong, light material.It can be deposited on the surface of glass to make mirrors, and also to make synthetic rubies and sapphires for lasers.Al is found in the environment in its natural forms or as a source of human contamination resulting from mining and smelting, activities that increase their distribution throughout the environment.Al occurs naturally only in compounds, never as a pure metal.Because of its strong affinity to oxygen, it is almost never found in the elemental state; instead it is found in oxides or silicates (WHO, 1997;Nayak, 2002).In nature, this trace element is found in its oxidized state Al 3+ (soluble toxic form of Al), which binds to others molecules like chloride, forming Aluminum chloride (AlCl 3 ) (Smith, 1996; WHO, 1997).Aluminum chloride (AlCl 3 ) is an important coagulant used in water treatment and purification (WHO, 1997; Zhang e Zhou, 2005) being another source for exposure.Two of the most common compounds are potassium aluminum sulfate (KAl(SO 4 ) 2 12H 2 O), and aluminum oxide (Al 2 O 3 ).Although aluminum is a widespread element, almost all metallic aluminium is produced from the ore bauxite (AlO x (OH) 3-2x ).Bauxite is a complicated mixture of compounds consisting of 55% of aluminum, oxygen, and other elements (WHO, 1997;Nayak, 2002).Large reserves of bauxite are found in Australia, Brazil, Guinea, Jamaica, Russia, and the United States.No biological function of the element has been identified, whereas some aspects of its toxicity have been described (Berthon, 1996;Corain et al., 1996;Suwalsky et al., 2001).The exposure to this toxic metal occurs through air, food, water and it is also present in medical, cosmetic and environmental products (Berthon, 2002).Daily consumed of Al by food and beverages is 2.5 to 13 mg, where drinking water can contributes to 0.2 to 0.4 mg of Al daily.Drugs can contribute with increase levels of Al; antiacid drugs (2 tablets) can contribute up to 500 mg of Al (WHO, 1997).As the world becomes more industrialize, the chronic exposure to Al increases, increasing the risk for the development of neurodegenerative disorders like AD and PD.The period in human history beginning in about 1200 B.C. is called the Iron Age.Iron is a transition metal and normally does not occur as a free element (Meteoric origen) (ONeil, 1994).The most common ores of iron are hematite, or ferric oxide (Fe 2 O 3 ); limonite, or ferric oxide (Fe 2 O 3 ); magnetite, or iron oxide (Fe 3 O 4 ); and siderite, or iron carbonate (FeCO 3 ).An increasingly important source of iron is taconite.Taconite is a mixture of hematite and silica (sand).The largest iron resources in the world are in China, Russia, Brazil, Canada, How to referenceIn order to correctly reference this scholarly work, feel free to copy and paste

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