Vitamin E‐Mediated Modulation of Glutamate Receptor Expression in an Oxidative Stress Model of Neural Cells Derived from Embryonic Stem Cell Cultures

Abstract

Glutamate is the primary excitatory neurotransmitter in the central nervous system. Excessive concentrations of glutamate in the brain can be excitotoxic and cause oxidative stress, which is associated with Alzheimer's disease. In the present study, the effects of vitamin E in the form of tocotrienol-rich fraction (TRF) and alpha-tocopherol (α-TCP) in modulating the glutamate receptor and neuron injury markers in an in vitro model of oxidative stress in neural-derived embryonic stem (ES) cell cultures were elucidated. A transgenic mouse ES cell line (46C) was differentiated into a neural lineage in vitro via induction with retinoic acid. These cells were then subjected to oxidative stress with a significantly high concentration of glutamate. Measurement of reactive oxygen species (ROS) was performed after inducing glutamate excitotoxicity, and recovery from this toxicity in response to vitamin E was determined. The gene expression levels of glutamate receptors and neuron-specific enolase were elucidated using real-time PCR. The results reveal that neural cells derived from 46C cells and subjected to oxidative stress exhibit downregulation of NMDA, kainate receptor, and NSE after posttreatment with different concentrations of TRF and α-TCP, a sign of neurorecovery. Treatment of either TRF or α-TCP reduced the levels of ROS in neural cells subjected to glutamate-induced oxidative stress; these results indicated that vitamin E is a potent antioxidant.

The preventative effect of α-tocopherol on spinal epidural fibrosis after laminectomy in a rat model.

“…These mechanisms indicate the importance of the mitochondrial pathway in apoptotic effects of α-TCP and also the possibility that Cyt c-dependent pathways may be used. Apoptotic effects of α-TCP on different cell lines attenuated some more experimental studies in the literature (14).…”

Neuroprotective Effect of Tricyclic Pyridine Alkaloids from Fusarium lateritium SSF2, against Glutamate-Induced Oxidative Stress and Apoptosis in the HT22 Hippocampal Neuronal Cell Line

“…It is well known that the rapid ROS, including superoxide triggered by glutamate can lead to neuronal cell death [ 21 ], and apoptosis pathways [ 22 ]. Earlier studies reported that antioxidants exert neuroprotective effects by blocking oxidative stress and apoptosis in vitro and in vivo [ 23 ]. In the present study, in the presence of ROS generated by glutamate, fluorescent dichlorofluorescein was increased, but it was significantly attenuated when HT22 cells were co-treated with 4,6′-anhydrooxysporidinone.…”

Effect of Oral Vitamin E on Oxidative Stress in Diabetic Kidney Disease：A Protocol of Systematic Review and Meta-Analysis

“…As a lipid soluble potent antioxidant [7], vitamin E can indirectly regulate and increase the activity of gSH-PX in cells, thus inhibiting lipid peroxidation of the bio lm and maintaining the structural integrity of bio lm. Clinical studies have demonstrated that vitamin E coated dialyzers can improve chronic in ammation and oxidative stress without affecting dialysis adequacy [8], and animal studies have also con rmed the antioxidant and anti-apoptotic properties of vitamin E, which may protect diabetic rats from myocardial and renal damage [9] and reduce the autophagy stress response [10].…”