| Aluminum is the third most abundant element on the earth's crust. However, despite its abundance, a biological function has not been discovered. On the contrary, a role for aluminum salts in dialysis encephalopathy, microcytic anemia, osteomalacia and more controversially in Alzheimer's disease (AD) has been proposed. Since inflammation is one of the features found in the brain of patients with neurodegenerative disorders such as AD, the effect of aluminum salts on markers of inflammation in the central nervous system (CNS) was investigated. In the brains of mice chronically exposed to aluminum lactate in drinking water there was selective elevation of several inflammatory parameters. It has also been suggested that pro-oxidant metals such as copper may also be involved in the pathogenesis of AD and thus interactions between aluminum and copper ions were sought. It was hypothesized that the neuroinflammatory & oxidative potential of aluminum salts may be enhanced by co-exposure with the pro-oxidant metal, cupric sulfate. While cupric sulfate-induced oxidative stress was enhanced by co-exposure to aluminum sulfate in glial cells, inflammatory markers induced by either metal were not further potentiated by exposure to both aluminum and copper salts. In mice treated with aluminum lactate in drinking water there was an increase in oxidative and inflammatory markers in the brain. Cupric sulfate did not have an effect on this response. Thus, in the in vitro and in vivo studies presented here, oxidative stress contributes minimally to the capability of aluminum salts to produce an inflammatory response. However, chronic exposure to low concentrations of aluminum salts may cause a subtle but prolonged upregulation of oxidative events and a change towards a chronic inflammatory status in the brain which may ultimately result in the onset and/or progression of AD. |
