TY - JOUR
T1 - Antioxidants attenuate acute toxicity of tumor necrosis factor-α induced by brain injury in rat
AU - Trembovler, Victoria
AU - Beit-Vannai, Elie
AU - Younis, Firas
AU - Gallily, Ruth
AU - Horowitz, Michal
AU - Shohami, Esther
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032777720&partnerID=8YFLogxK
U2 - 10.1089/107999099313640
DO - 10.1089/107999099313640
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C2 - 10454350
AN - SCOPUS:0032777720
SN - 1079-9907
VL - 19
SP - 791
EP - 795
JO - Journal of Interferon and Cytokine Research
JF - Journal of Interferon and Cytokine Research
IS - 7
ER -