Cytoprotective Effect of Tocotrienol-Rich Fraction and α-Tocopherol Vitamin E Isoforms Against Glutamate-Induced Cell Death in Neuronal Cells

Int J Vitam Nutr Res. 2014;84(3-4):140-51. doi: 10.1024/0300-9831/a000201.


Glutamate is the major mediator of excitatory signals in the mammalian central nervous system. Extreme amounts of glutamate in the extracellular spaces can lead to numerous neurodegenerative diseases. We aimed to clarify the potential of the following vitamin E isomers, tocotrienol-rich fraction (TRF) and α-tocopherol (α-TCP), as potent neuroprotective agents against glutamate-induced injury in neuronal SK-N-SH cells. Cells were treated before and after glutamate injury (pre- and post-treatment, respectively) with 100-300 ng/ml TRF/α-TCP. Exposure to 120 mM glutamate significantly reduced cell viability to 76% and 79% in the pre- and post-treatment studies, respectively; however, pre- and post-treatment with TRF/α-TCP attenuated the cytotoxic effect of glutamate. Compared to the positive control (glutamate-injured cells not treated with TRF/α-TCP), pre-treatment with 100, 200, and 300 ng/ml TRF significantly improved cell viability following glutamate injury to 95.2%, 95.0%, and 95.6%, respectively (p<0.05).The isomers not only conferred neuroprotection by enhancing mitochondrial activity and depleting free radical production, but also increased cell viability and recovery upon glutamate insult. Our results suggest that vitamin E has potent antioxidant potential for protecting against glutamate injury and recovering glutamate-injured neuronal cells. Our findings also indicate that both TRF and α-TCP could play key roles as anti-apoptotic agents with neuroprotective properties.

Keywords: TRF; cell death; glutamate; neuronal cell; α-TCP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Death / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Free Radicals / antagonists & inhibitors
  • Glutamic Acid / toxicity*
  • Humans
  • Malondialdehyde / analysis
  • Membrane Potential, Mitochondrial / drug effects
  • Microscopy, Electron, Scanning
  • Neuroblastoma
  • Neurodegenerative Diseases / prevention & control
  • Neurons / drug effects*
  • Neurons / physiology
  • Neurons / ultrastructure
  • Neuroprotective Agents
  • Tocotrienols / administration & dosage*
  • alpha-Tocopherol / administration & dosage*


  • Antioxidants
  • Free Radicals
  • Neuroprotective Agents
  • Tocotrienols
  • Glutamic Acid
  • Malondialdehyde
  • alpha-Tocopherol