Abstract
The overexposure to nickel due to the extensive use of it in modern technology remains a major public health concern. The mechanisms of pathological effects of this metal remain elusive. The present study was devoted to evaluate the effect of nickel on the oxidative state of the brain cells of mice and to assess whether zinc as redox state modulator could efficiently protect cells against nickel's neurotoxicity. As oxidative stress biomarkers in the present study, we have measured the concentrations of reduced glutathione, metallothioneins, and malondialdehyde and the activity of the enzyme δ-aminolevulinate dehydratase. For the single metal exposure, mice were i.p. injected once with solutions of NiCl2 and/or ZnSO4; repeated exposure was performed i.p. injecting metal salt solutions for 14 days (once a day). The control mice received i.p. injections of saline. Results of our study demonstrate that single and 14 days of Ni2+ exposure decreased reduced glutathione and increased malondialdehyde contents in the brain of mice. Repeated Ni2+ administration significantly inhibited δ-aminolevulinate dehydratase while increasing brain metallothionein concentration at both exposure periods. Zinc exhibited a protective effect against nickel-induced glutathione and lipid peroxidation in brain cells of mice at both intervals of time, while repeated exposure to this metal significantly raised the brain metallothionein content. Repeated Zn2+ pretreatment protected δ-aminolevulinate dehydratase from Ni2+-induced inhibition and significantly increased metallothionein concentration at both investigated time intervals.
Highlights
Nickel is a transition metal found in the Earth’s crust in combination most usually with iron, sulphur, oxygen, or arsenic
In order to assess the antioxidant status of the brain, we have evaluated the alterations of GSH, MDA, and MT contents as well as the activity of ALAD as reliable oxidative stress biomarkers, since these parameters are closely related and interdependent [26, 35,36,37,38]
In the healthy brain, where the redox balance is maintained, the resulting reactive oxygen species (ROS) are beneficial and even necessary; redox balance disturbance causes a condition known as oxidative stress, which is closely related to neurodegeneration [39, 40]
Summary
Nickel is a transition metal found in the Earth’s crust in combination most usually with iron, sulphur, oxygen, or arsenic. In combination with some other metals, Ni is used to form alloys, to produce coins, ceramics, steel, jewellery, battery, medical devices, electroplating, orthodontic appliances, and many others [3, 4]. Ni has been added to the list of essential trace elements quite recently; there exists a substantial list of Ni-required enzymes [2, 7, 8] It was considered as an essential element based on reports of Ni necessity for plants and deficiency in some animal species; the functional importance of Ni and its physiological relevance in humans yet remain unclear, and deficiency was never reported either [2, 3, 9]. Healthy human body contains up to 10 mg of Ni and some data suggest that it might be involved primarily in the regulation of liver function, related to normal growth, Fe homeostasis, and red blood cell production, the exact role of Ni is still unclear [10, 11]
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