Effects of Tert-Butylhydroquinone on Intestinal Inflammatory Response and Apoptosis following Traumatic Brain Injury in Mice

Abstract

Traumatic brain injury (TBI) can induce intestinal inflammatory response and mucosal injury. Antioxidant transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown in our previous studies to prevent oxidative stress and inflammatory response in gut after TBI. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), an Nrf2 inducer, can protect against TBI-induced intestinal inflammatory response and mucosal injury in mice. Adult male ICR mice were randomly divided into three groups: (1) sham + vehicle group, (2) TBI + vehicle group, and (3) TBI + tBHQ group (n = 12 per group). Closed head injury was adopted using Hall's weight-dropping method. Intestinal mucosa apoptosis and inflammatory-related factors, such as nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1), were investigated at 24 h after TBI. As a result, we found that oral treatment with 1% tBHQ prior to TBI for one week markedly decreased NF-κB activation, inflammatory cytokines production, and ICAM-1 expression in the gut. Administration of tBHQ also significantly attenuated TBI-induced intestinal mucosal apoptosis. The results of the present study suggest that tBHQ administration could suppress the intestinal inflammation and reduce the mucosal damage following TBI.

Protective effect of nuclear factor E2-related factor 2 on inflammatory cytokine response to brominated diphenyl ether-47 in the HTR-8/SVneo human first trimester extravillous trophoblast cell line

“…As such, decreased NF-κB activity partially explains the anti-inflammatory effect of tBHQ in the present study. These findings are consistent with previous studies showing that tBHQ or sulforaphane decrease NF-κB activation, production of inflammatory cytokines (TNF-α, IL-1β, and IL-6), COX-2 expression, and PGE2 release in vivo and in vitro (Heiss et al , 2001; Jin et al , 2010; Khodagholi and Tusi, 2011; Koh et al , 2009). However, to the best of our knowledge, the present study is the first to report the protective role of Nrf2 activation on toxicant-stimulated inflammatory responses in human placental cells.…”

tert-Butylhydroquinone (tBHQ) protects hepatocytes against lipotoxicity via inducing autophagy independently of Nrf2 activation

“…In kidney, tBHQ protected against ischemia-reperfusion injury [43]. Moreover, a recent study showed that tBHQ administration suppressed the intestinal inflammation and reduced the mucosal damage following traumatic brain injury [44]. Our study was initially designed to test this hypothesis using tBHQ as an Nrf2 inducer in AML-12 cells, a non-transformed murine hepatocyte cell line.…”

Interplay between VEGF and Nrf2 regulates angiogenesis due to intracranial venous hypertension

“…However, upon exposure to oxidative stress, Nrf2 is released from Keap1, translocates into the nucleus, and stimulates antioxidant response element (ARE)-dependent phase II gene expression891011. Preliminary studies in our laboratory explored the protection of Nrf2 in traumatic brain injury1213141516. An increasing number of studies supporting the pivotal role of Nrf2 in angiogenesis show that Nrf2 may promote vascular development via protection of retina from hyperoxia-induced oxidative stress17; these studies also indicate that Nrf2 blockade suppresses tumor cell angiogenesis and migration in vivo and in vitro 181920.…”