Abstract | BACKGROUND:
Traumatic brain injury (TBI) is a worldwide health problem, identified as a major cause of death and disability. Increasing evidence has shown that oxidative stress plays an important role in TBI pathogenesis. The antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), is a known mediator in protection against TBI-induced brain damage. The objective of this study was to test whether tert-butylhydroquinone ( tBHQ), a novel Nrf2 activator, can protect against TBI-induced oxidative stress. METHODS: RESULT: The NOX2 protein level was increased fivefold in the TBI + vehicle group, whereas pretreatment with tBHQ markedly attenuated the NOX2 protein expression relative to that in the TBI + vehicle group. TBI increased Nrf2 formation by 5% compared with the sham group, whereas treatment with tBHQ further upregulated the Nrf2 protein level by 12% compared with the sham group. The level of the oxidative damage marker malondialdehyde was reduced by 29% in the TBI + tBHQ group compared with the TBI + vehicle group, Moreover, pretreatment with tBHQ significantly increased the antioxidant enzyme superoxide dismutase activity. Administration of tBHQ also significantly decreased TBI-induced brain edema and neurologic deficits. CONCLUSIONS: Pretreatment with tBHQ effectively attenuated markers of cerebral oxidative stress after TBI, thus supporting the testing of tBHQ as a potential neuroprotectant and adjunct therapy for TBI patients.
|
Authors | Xin-Yu Lu, Han-dong Wang, Jian-Guo Xu, Ke Ding, Tao Li |
Journal | The Journal of surgical research
(J Surg Res)
Vol. 188
Issue 1
Pg. 206-12
(May 01 2014)
ISSN: 1095-8673 [Electronic] United States |
PMID | 24387843
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2014 Elsevier Inc. All rights reserved. |
Chemical References |
- Antioxidants
- Hydroquinones
- Membrane Glycoproteins
- NF-E2-Related Factor 2
- Nfe2l2 protein, mouse
- Malondialdehyde
- 2-tert-butylhydroquinone
- Superoxide Dismutase
- Cybb protein, mouse
- NADPH Oxidase 2
- NADPH Oxidases
|
Topics |
- Animals
- Antioxidants
(therapeutic use)
- Brain Damage, Chronic
(etiology, prevention & control)
- Brain Edema
(etiology, prevention & control)
- Brain Injuries
(complications, drug therapy)
- Drug Evaluation, Preclinical
- Hydroquinones
(therapeutic use)
- Male
- Malondialdehyde
(metabolism)
- Membrane Glycoproteins
(metabolism)
- Mice
- NADPH Oxidase 2
- NADPH Oxidases
(metabolism)
- NF-E2-Related Factor 2
(metabolism)
- Neurologic Examination
- Oxidative Stress
(drug effects)
- Random Allocation
- Superoxide Dismutase
(metabolism)
|