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.

Modulation of 14C‐labeled glucose metabolism by zinc during aluminium induced neurodegeneration

“…This increase in 14 C‐glucose uptake indicates the increase in the requirement for glucose by neurodegenerative cells following Al treatment. These observations are well supported by our carbohydrate metabolism and histology findings, which also showed glucose‐deficient conditions in Al‐induced degenerative neurons (Singla and Dhawan, ). Furthermore, this trivalent metal has a pro‐oxidant activity, so it could have triggered oxidative stress either directly or indirectly by interacting with various proteins and molecules involved in energy metabolism (Yoshino et al, ; Gómez et al, ).…”

“…Furthermore, combined treatment with Zn resulted in appreciable moderation in the uptake and turnover of glucose in Al‐treated animals, which could be due to upregulation of various metabolic enzymes that were inhibited by Al. In addition, earlier studies from our laboratory have shown hypoxia‐induced neuronal death after Al exposure; appreciable improvement was shown following Zn cotreatment (Bhalla and Dhawan, ; Bhalla et al, ; Bhasin et al, ; Singla and Dhawan, ). These observations clearly demonstrate that Zn supplementation results in remarkable improvement in energy metabolic processes, suggesting its protective effect in replenishing energy within neurons.…”

“…These findings indicate that Al causes a drop in energy metabolism in the brain, given that altered glucose uptake is an indicator of metabolic stress. However, Zn supplementation has been proved to be beneficial because it is able to decrease the elevated glucose uptake and improve the neurohistoarchitecture, thereby suggesting its prophylactic potential in physiological systems (Singla and Dhawan, ,c). Therefore, the results of this study clearly indicate that Zn can be regarded as a neuroprotective candidate in alleviating Al‐altered glucose metabolism in rat brain.…”

Physical, Chemical, and Immunohistochemical Investigation of the Damage to Salivary Glands in a Model of Intoxication with Aluminium Citrate

“…The harmful effects of Al are known to be neutralized by zinc [ 48 , 49 ], which is an essential metal for cellular function. Zinc is regulated by metallothionein [ 43 ].…”

“…Zinc is regulated by metallothionein [ 43 ]. Al leads to an increase of intracellular zinc concentrations [ 49 ]. Therefore, if the zinc content is high there will also be high contents of metallothionein, since this is the protein that regulates zinc entry into the cell, reducing the toxic effects of Al.…”