title: Tert-butylhydroquinone protects the spinal cord against inflammatory response produced by spinal cord injury.
abstract: Antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown in our previous studies to play an important role in protection against spinal cord injury (SCI) induced inflammatory response. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), a novel Nrf2 activator, can protect the spinal cord against SCI-induced inflammatory damage. Adult male Sprague-Dawley rats were subjected to laminectomy at T8-T9 and compression with a vascular clip. Three groups were analyzed: a sham group, a SCI group, and a SCI+rhEPO group (n=16 per group). We measured Nrf2 and nuclear factor kappa B (NF-κB) binding activities by an electrophoretic mobility shift assay (EMSA). We also measured the concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) by an enzyme-linked immunosorbent assay (ELISA); we also measured hindlimb locomotion function by the Basso, Beattie, and Bresnahan (BBB) rating, spinal cord edema by wet/dry weight method, and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis. The results showed that the induction of the Nrf2 activity by tBHQ markedly decreased NF-κB activation and inflammatory cytokines production in the injured spinal cord. Administration of tBHQ also significantly attenuated SCI induced hindlimb locomotion deficits, spinal cord edema, and apoptosis. To conclude, pre-treatment with tBHQ could attenuate the spinal cord inflammatory response after SCI.
authors.affiliation: Department of Neurosurgery, Drum Tower Hospital, Medical School of Nanjing University, 321 Zhongshan Road, Nanjing 210008, Jiangsu Province, China; phone: 86 25 83106666; njneirosurgery@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.forename: Hongbin
authors.initials: H
authors.lastname: Ni
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Hou
authors.forename: Xing
authors.initials: X
authors.lastname: Ming
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Baoyu
authors.initials: B
authors.lastname: Yuan
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Jiang
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
authors.forename: Weibang
authors.initials: W
authors.lastname: Liang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D006873:Hydroquinones / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011485:Protein Binding / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D013119:Spinal Cord Injuries / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D016207:Cytokines; D006873:Hydroquinones; D018836:Inflammation Mediators; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D018696:Neuroprotective Agents; D004247:DNA; C018855:2-tert-butylhydroquinone
keywords: Nrf2; inflammatory response; spinal cord injury; tBHQ