Tert-butylhydroquinone ameliorates doxorubicin-induced cardiotoxicity by activating Nrf2 and inducing the expression of its target genes
- Am J Transl Res. 2015 Oct 15;7(10):1724-35.
- 1. Department of Spine Surgery, The Third Hospital of Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
- 2. The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Department of Pharmacology, Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
- 3. Department of Toxicology, Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
- 4. Department of Neurology, The Second Hospital of Hebei Medical University Shijiazhuang, Hebei Province, 050017, China.
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
Nad(p)h: 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.