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Neuro-recovery of vitamin E in high glutamate-induced oxidative stress neural cells derived from embryonic stem cell culture model

Nurliyana Najwa Md Razip1, Afifah Abd Jalil1, Norshariza Nordin1, 2, Amirah Salwani Zaulkffli3, Nur'Izzati Mansor1, 2 and Huzwah Khaza'Ai1*
  • 1 Department of Biomedical Sciences, Faculty of Medicine and Health sciences, University of Putra Malaysia, Malaysia
  • 2 Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Putra Malaysia University, Malaysia
  • 3 Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia

Background Excitatory glutamatergic of neurotransmitter is essential for neuronal plasticity in the brain. However, excessive glutamate-binding activity over-stimulates the postsynaptic receptors in neuron cause excitotoxic and oxidative stress, which is associated with the pathogenesis of Alzheimer’s Disease (AD). High level of reactive oxygen species explicates neuro-injury due to lack of antioxidant. Further study elucidates the potential of vitamin E against the neuronal injury mechanisms. Methods Neural derived embryonic stem cells were exposed to a toxic concentration of glutamate (60 mM) enough to demonstrate the injured neuronal model. The potential of vitamin E [tocotrienol rich fraction (TRF) and alpha-tocopherol (alpha-TCP)] in modulating oxidative stress and recovery process upon glutamate toxicity was elucidated. The expression of glutamate receptors (N-methyl-d-aspartate receptors, NMDAR and kainate receptors) and neuron injury marker (neuron-specific enolase, NSE) were quantified with real-time polymerase chain reaction (RT-PCR) as a biomarker of the recovery process. Results Supplementation of vitamin E at 100, 200 and 300 ng/mL reduced 90% rate of overstimulation NMDA-1 (GluN-1) compared to positive control with fold ratio 0.347±0.03, 0.195±0.04 and 0.083±0.01, respectively. Gluk1 is a kainate receptor reduced with the fold ratio of 0.594±0.16, 0.320±0.02 and 0.291±0.07 respectively compared to positive control. NSE decreased significantly with the fold ratio at 0.525±0.03, 0.514±0.02 and 0.605±0.11 respectively. Meanwhile, alpha-TCP treatment at concentration of 100, 200 and 300 ng/ml on glutamate toxicity model indicated the significant reduction of GluN-1 (0.646+0.06, 0.583+0.01 and 0.530+0.09) respectively, Gluk1 indicates significant reduction at 100 and 200 ng/ml at fold ratio of 0.614±0.09 and 0.502±0.04 and NSE (0.468±0.08, 0.460±0.1 and 0.782±0.12) fold ratio. Conclusion Both isomers of vitamin E in the form of tocotrienols and tocopherols are suggested as a potent antioxidant that quenching radicals hence counter-regulate the excessive glutamate stimulated receptors which help to reduce AD risk.

Acknowledgements

This research was financially supported by the Putra Graduate Initiative (Vote 9464900) at Universiti Putra Malaysia.

References

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Keywords: Glutamate, neuronal injury, Oxidative Stress, Alzheimer ' s disease, Vitamin E

Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019.

Presentation Type: Poster Presentation

Topic: Neurodegenerative diseases

Citation: Md Razip N, Abd Jalil A, Nordin N, Zaulkffli A, Mansor N and Khaza'Ai H (2019). Neuro-recovery of vitamin E in high glutamate-induced oxidative stress neural cells derived from embryonic stem cell culture model. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00072

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Received: 30 Sep 2018; Published Online: 17 Jan 2019.

* Correspondence: Dr. Huzwah Khaza'Ai, Department of Biomedical Sciences, Faculty of Medicine and Health sciences, University of Putra Malaysia, Kuala Lumpur, 43400, Malaysia, huzwah@upm.edu.my