title: Tert-butylhydroquinone ameliorates doxorubicin-induced cardiotoxicity by activating Nrf2 and inducing the expression of its target genes.
abstract: Oxidative stress plays an important role in doxorubicin (DOX)-induced cardiotoxicity. Nuclear factor E2-related factor-2 (Nrf2) is a transcription factor that orchestrates the antioxidant and cytoprotective responses to oxidative stress. In the present study, we tested whether tert-butylhydroquinone (tBHQ) could protect against DOX-induced cardiotoxicity in vivo and, if so, whether the protection was associated with the up-regulation of the Nrf2 pathway. The results showed that treatment with tBHQ significantly decreased the DOX-induced cardiac injury in wild-type mice. Moreover, tBHQ ameliorated the DOX-induced oxidative stress and apoptosis. Further studies suggested that tBHQ increased the nuclear accumulation of Nrf2 and the Nrf2-regulated gene expression, including heme oxygenase-1 (HO-1) and
  quinone oxido-reductase-1 (NQO-1) expression. Knocking out Nrf2 in mice abolished the protective effect of tBHQ on the DOX-induced cardiotoxicity. These results indicate that tBHQ has a beneficial effect on DOX-induced cardiotoxicity, and this effect was associated with the enhanced expression of Nrf2 and its downstream antioxidant genes, HO-1 and NQO-1.
authors.affiliation: Department of Spine Surgery, The Third Hospital of Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
authors.forename: Lin-Feng
authors.initials: LF
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Department of Pharmacology, Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
authors.forename: Su-Wen
authors.initials: SW
authors.lastname: Su
authors.affiliation: Department of Toxicology, Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Toxicology, Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Toxicology, Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Niu
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
authors.forename: Yan-Su
authors.initials: YS
authors.lastname: Guo
authors.affiliation: Department of Neurology, The Second Hospital of Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Li
authors.affiliation: Department of Toxicology, Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Jiang
authors.affiliation: Department of Toxicology, Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Toxicology, Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
authors.forename: Hui-Cai
authors.initials: HC
authors.lastname: Guo
keywords: Doxorubicin; NAD(P)H:quinone oxido-reductase-1; cardiotoxicity; heme oxygenase-1; nuclear factor erythroid 2-related factor 2; tert-butylhydroquinone