Neuroprotective effect of vitamin E isoforms against chronic alcohol-induced peripheral neurotoxicity: possible involvement of oxidative-nitrodative stress

Phytother Res. 2012 Nov;26(11):1738-45. doi: 10.1002/ptr.4635. Epub 2012 Mar 15.


Small-fiber painful peripheral neuropathy is one of the long-term complications of alcohol for which there is no reliable successful therapy available. The precise mechanisms by which chronic alcohol consumption produces peripheral nerve fiber damage and loss remain unclear. Emerging data from clinical and preclinical studies suggest that increased oxidative-nitrodative stress mediated release of proinflammatory cytokines from damaged neural tissues may play a central role in the pathogenesis of alcoholic neuropathy. The present study investigated the effect of both the isoforms of vitamin E (α-tocopherol and tocotrienol) against chronic alcohol-induced peripheral neuropathy in rats. Ethanol treated rats showed a significant decrease in paw-withdrawal threshold in both Randall-Selitto and von-Frey hair tests along with a significant reduction in tail flick latency in the tail-immersion test. A decreased pain threshold was associated with significant alterations in oxidative-nitrodative stress markers and an increase in proinflammatory cytokines (TNF-α and IL-1β). The 4-week treatment with tocotrienol significantly ameliorated behavioral, biochemical and molecular alterations in alcohol treated rats. However, α-tocopherol failed to produce any protective effect. The results of the present study suggest that oxidative-nitrodative stress mediated cytokine signaling may be responsible for alcohol-induced peripheral neurotoxicity and tocotrienol treatment might be beneficial in chronic alcoholics exhibiting neuropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholic Neuropathy / drug therapy*
  • Animals
  • Interleukin-1beta / metabolism
  • Lipid Peroxidation
  • Male
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Pain Measurement
  • Rats
  • Rats, Wistar
  • Sciatic Nerve / drug effects
  • Tocotrienols / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism
  • alpha-Tocopherol / pharmacology*


  • Interleukin-1beta
  • Neuroprotective Agents
  • Tocotrienols
  • Tumor Necrosis Factor-alpha
  • alpha-Tocopherol