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Biol Trace Elem Res (2016) 174:410418 DOI 10.1007/s12011-016-0742-z
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Web End = Vinpocetine and Vasoactive Intestinal Peptide Attenuate Manganese-Induced Toxicity in NE-4C Cells
Saylav Bora1 & Mumin Alper Erdogan1 & Gliz Armagan2 & Elvin Sevgili2 & Taner Dagc1
Received: 16 March 2016 /Accepted: 11 May 2016 /Published online: 20 May 2016 # Springer Science+Business Media New York 2016
Abstract Increased concentration of manganese (Mn) in the brain is known to be associated with excitotoxicity and neuroinflammation. Vinpocetine, an alkaloid derived from the plant Vinca minor L., basically shows its effect via phosphodiesterase inhibition and voltage-dependent Na+ channels. Vasoactive intestinal peptide (VIP) has gastrointestinal, vaso-motor, muscular, and neuroprotective effects. The aim of this study was to examine the potential protective effects of vinpocetine and VIP against Mn toxicity in NE-4C neural stem cells (NSCs). VIP treatment at 1 M and vinpocetine treatment at 2 M concentrations were sufficient to yield maximum protection, and these concentrations were adopted in the following experiments. In this study, Mn treatment significantly increased lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) production, and triggered cell death in NE-4C cultures. However, significant reduction in LDH release was observed following vinpocetine or VIP treatments when compared with control. Similar to these findings, vinpocetine or VIP treatments significantly reduced membrane degradation induced by Mn (p < 0.001). Moreover, vinpocetine attenuated Mn-induced decrease of mitochondrial membrane potential. Similarly, proapoptotic protein bax and ROS production significantly decreased in cells after incubation with vinpocetine (p = 0.01) or VIP in the presence of Mn (p < 0.001). Our study provides the evidence that both vinpocetine and VIP may exert protective effects via
modulating oxidative stress and apoptosis in Mn-induced neurodegeneration in NE-4C cells.
Keywords Manganese . NE-4C cells . Vinpocetine . Vasoactive intestinal peptide . Apoptosis
Introduction
Manganese (Mn) is the most commonly used metal in the world following iron, aluminum, and copper. Ninety-four percent of Mn is used in steel, battery refining industries, and also in imaging techniques as part of health sector [1]. Mn is an essential metal in the organism. It has many roles in metabolic processes in the biological system. It is a cofactor for many enzymatic activities [2]. Normally, there is a small amount of Mn in the...