Regulatory role of zinc during aluminium‐induced altered carbohydrate metabolism in rat brain

Abstract

Aluminium is considered an environmental neurotoxicant and causes many neurological disorders, whereas zinc is vital for many biological functions. The present study was carried out to investigate the role of Zn, if any, in mitigating the adverse effects inflicted by Al on carbohydrate metabolism in rat brain. Male Sprague-Dawley rats weighing 140-160 g were divided into four different groups: normal control, Al-treated (100 mg/kg b.w./day in drinking water via oral gavage), Zn-treated (227mg/liter in drinking water), and combined Al- and Zn-treated rats. All the treatments were continued for 2 months, and their effects on carbohydrate-metabolizing enzymes were studied. Additionally, expressions of the proteins glycogen synthase kinase-3 (GSK3) and protein phosphatase (PP1), which help in regulating carbohydrate energy metabolism, were also studied. Al treatment resulted in increased activities of the glucose-6-phosphatase (G6P), glucose-6-isomerase (G6I), and lactate dehydrogenase (LDH), whereas the activities of hexokinase and succinate dehydrogenase (SDH) and glycogen content were decreased. Moreover, no significant change was observed in the biochemical parameters upon Zn supplementation alone. However, Zn supplementation to Al-treated rats was able to reduce significantly the Al-induced increased activities of G6P, G6I, and LDH, but it elevated the levels of hexokinase, SDH, and glycogen. Furthermore, Al treatment increased the protein expression of GSK3 and decreased the PP1 expression, which were found to be reversed upon Zn administration. Hence, Zn is effective in regulating theAl-induced alterations in carbohydrate metabolism.

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, high Al content in the cellular environment might have caused the negative influence on the generation of ATP in neurons. Our previous observations also illustrated the negative impact of Al on the ATP‐producing machinery in oxygen‐consuming cells (Singla and Dhawan, ). Al treatment inhibited the activities of Ca 2+ ATPase and Na + /K + ATPase by directly interacting at the active binding sites of ATPases, indicating that Al altered cellular metabolism (Kaur and Gill, ; Silva et al, ; Singla and Dhawan, ).…”

“…Animals in group I served as normal controls and were fed with a normal diet and water ad libitum throughout the period of experimentation. Animals in group II were given Al in the form of aluminium chloride (AlCl 3 dissolved in drinking water) orally at a dose of 100 mg/kg body weight (Singla and Dhawan, ). Group III animals were given Zn in the form of ZnSO 4 · 7H 2 O in drinking water every day at a dose of 227 mg/liter of water (Goel et al, ).…”

“…Reports have suggested that chronic treatment of animals with Al is associated with neurobehavioral, neurochemical, and neuropathological alterations (Prakash et al, ; Di Paolo et al, ; Lakshmi et al, ). Several studies have shown that Al can disturb the normal functioning of apoptotic machinery, the glutathione system, and carbohydrate and lipid metabolism in the brain (Flora et al, ; Singla and Dhawan, ; Oshima et al, ; Zhang et al, ; Lakshmi et al, ). Al has been suggested to cause impairment in the central nervous system by interfering with calcium, zinc (Zn), and iron homeostasis in the brain (Kawahara, ; Drago et al, ; Wang et al, ).…”

Health Effects of Metals in Particulate Matter

“…In previous studies it has been reported that aluminum inhalation induced altered of expressions of glycogen synthase kinase-3 (GSK3) and protein phosphatase (PP1), which help in the regulation of carbohydrate metabolism in the rat's brain [87]. Mercury exposures in male marmoset monkey showed deposits of Hg in ventral horn motor neuron and atrophy of large myelinated motor axon [88].…”