Antioxidants attenuate acute toxicity of tumor necrosis factor-alpha induced by brain injury in rat

V Trembovler, E Beit-Yannai, F Younis, R Gallily, M Horowitz, E Shohami

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Tumor necrosis factor-alpha alpha (TNF-alpha) and reactive oxygen species (ROS) are produced in the brain after traumatic injury and have deleterious effects. In a rat model of closed head injury (CHI), the synthetic antioxidant from the nitroxide family, Tempol, improved recovery and protected the blood-brain barrier. Similar protection was found after CHI in heat-acclimated rats, in which the endogenous antioxidants have been shown to be elevated after CHI. The present study examined the relationship between TNF-alpha and ROS after CHI, namely, whether after CHI, antioxidants that afforded cerebroprotection also attenuated brain levels of TNF-alpha. Three groups of rats were subjected to CHI: (1) control, nontreated, (2) Tempol-treated, and (3) heat-acclimated (30 days at 34 degrees C). Four hours after injury (time for peak production of TNF-alpha), the activity of TNF-alpha was measured. Although clinical recovery was facilitated in rats of the two treated groups, TNF-alpha activity was as high as in the traumatized, untreated rats. Moreover, direct injection of TNF-alpha into mouse brain induced disruption of the blood-brain barrier, indicating its acute harmful effect. This toxic effect was attenuated by before and after treatment with Tempol. Our results support the hypothesis that in vivo antioxidants neutralize TNF-alpha toxicity, probably by interfering with activation of the transcription factor NF-kappa-B.

Original languageEnglish GB
Pages (from-to)791-5
Number of pages5
JournalJournal of Interferon and Cytokine Research
Issue number7
StatePublished - Jul 1999


  • Analysis of Variance
  • Animals
  • Antioxidants/therapeutic use
  • Blood-Brain Barrier/drug effects
  • Brain Injuries/drug therapy
  • Cyclic N-Oxides/therapeutic use
  • Head Injuries, Closed/complications
  • Hot Temperature
  • Male
  • Rats
  • Rats, Inbred Strains
  • Reactive Oxygen Species/metabolism
  • Spin Labels
  • Tumor Necrosis Factor-alpha/biosynthesis


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