Tocotrienol prevents AAPH-induced neurite degeneration in neuro2a cells

Redox Rep. 2013;18(6):238-44. doi: 10.1179/1351000213Y.0000000065.


Objectives: Reactive oxygen species induce neurite degeneration before inducing cell death. However, the degenerative mechanisms have not yet been elucidated. While tocotrienols have a known neuroprotective function, the underlying mechanism remains unclear and may or may not involve antioxidant action. In this study, we hypothesize that free radical-derived membrane injury is one possible mechanism for inducing neurite degeneration. Therefore, we examined the potential neuroprotective effect of tocotrienols mediated through its antioxidant activity.

Methods: Mouse neuroblastoma neuro2a cells were used to examine the effect of the water-soluble free radical generator 2,2'-azobis(2-methylpropionamide) dihydrochloride (AAPH) on neurite dynamics. After 24 hours of AAPH treatment, cell viability, neurite number, and the number of altered neurites were measured in the presence or absence of α-tocotrienol.

Results: Treatment of neuro2a cells with a low concentration of AAPH induces neurite degeneration, but not cell death. Treatment with 5 µM α-tocotrienol significantly inhibited neurite degeneration in AAPH-treated neuro2a cells. Furthermore, morphological changes in AAPH-treated neuro2a cells were similar to those observed with colchicine treatment.

Conclusions: α-Tocotrienol may scavenge AAPH-derived free radicals and alkoxyl radicals that are generated from AAPH-derived peroxyl radicals on cell membranes. Therefore, α-tocotrienol may have a neuroprotective effect mediated by its antioxidant activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidines / antagonists & inhibitors
  • Amidines / toxicity*
  • Animals
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Colchicine / pharmacology
  • Free Radical Scavengers / pharmacology
  • Mice
  • Neurites / drug effects*
  • Neurites / ultrastructure
  • Neuroprotective Agents / pharmacology*
  • Tocotrienols / pharmacology*


  • Amidines
  • Free Radical Scavengers
  • Neuroprotective Agents
  • Tocotrienols
  • 2,2'-azobis(2-amidinopropane)
  • tocotrienol, alpha
  • Colchicine