Zinc modulates aluminium-induced oxidative stress and cellular injury in rat brain.

Abstract

Dysregulation of metal homeostasis has been perceived as one of the key factors in the progression of neurodegeneration. Aluminium (Al) has been considered as a major risk factor, which is linked to several neurodegenerative diseases, especially Alzheimer's disease, whereas zinc (Zn) has been reported as a vital dietary element, which regulates a number of physiological processes in central nervous system. The present study was conducted to explore the protective potential of zinc, if any, in ameliorating neurotoxicity induced by aluminium. Male Sprague Dawley rats received either aluminium chloride (AlCl3) orally (100 mg kg(-1) b.wt. per day), zinc sulphate (ZnSO4) at a dose level of 227 mg L(-1) in drinking water or combined treatment of aluminium and zinc for 8 weeks. Aluminium treatment significantly elevated the levels of lipid peroxidation and reactive oxygen species as well as the activities of catalase, superoxide dismutase and glutathione reductase, which however were decreased following Zn co-treatment of Al-treated rats. In contrast, Al treatment decreased the activities of glutathione-S-transferase as well as the levels of reduced glutathione, oxidised glutathione and total glutathione, but co-administration of Zn to Al-treated animals increased these levels. Furthermore, Al treatment caused a significant increase in the levels of Fe and Mn as well as of Al but decreased the Zn and metallothionein levels. In the Zn-supplemented animals, the levels of Al, Fe, Mn were found to be significantly decreased, whereas the levels of metallothionein as well as Zn were increased. Moreover, histopathological alterations such as vacuolization and loss of Purkinje cells were also evident following Al treatment, which showed improvement upon Zn supplementation. Therefore, zinc has the potential to alleviate aluminium-induced neurodegeneration.