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

Victoria Trembovler, Elie Beit-Vannai, Firas Younis, Ruth Gallily, Michal Horowitz, Esther Shohami*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Tumor necrosis factor-α alpha (TNF-α) 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-α and ROS after CHI, namely, whether after CHI, antioxidants that afforded cerebroprotection also attenuated brain levels of TNF-α. Three groups of rats were subjected to CHI: (1) control, nontreated, (2) Tempol- treated, and (3) heat-acclimated (30 days at 34°C). Four hours after injury (time for peak production of TNF-α), the activity of TNF-α was measured. Although clinical recovery was facilitated in rats of the two treated groups, TNF-α activity was as high as in the traumatized, untreated rats. Moreover, direct injection of TNF-α 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-α toxicity, probably by interfering with activation of the transcription factor NF-κ-B.

Original languageEnglish
Pages (from-to)791-795
Number of pages5
JournalJournal of Interferon and Cytokine Research
Volume19
Issue number7
DOIs
StatePublished - 1999

Fingerprint

Dive into the research topics of 'Antioxidants attenuate acute toxicity of tumor necrosis factor-α induced by brain injury in rat'. Together they form a unique fingerprint.

Cite this