Sulforaphane protects the liver against CdSe quantum dot-induced cytotoxicity

Wang, Wei, He, Yan, Yu, Guodong, Li, Baolong, Sexton, Darren W., Wileman, Thomas, Roberts, Alexandra A., Hamilton, Chris J., Liu, Ruoxi, Chao, Yimin, Shan, Yujuan and Bao, Yongping (2015) Sulforaphane protects the liver against CdSe quantum dot-induced cytotoxicity. PLoS One, 10 (9). ISSN 1932-6203

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      Abstract

      The potential cytotoxicity of cadmium selenide (CdSe) quantum dots (QDs) presents a barrier to their use in biomedical imaging or as diagnostic and therapeutic agents. Sulforaphane (SFN) is a chemoprotective compound derived from cruciferous vegetables which can up-regulate antioxidant enzymes and induce apoptosis and autophagy. This study reports the effects of SFN on CdSe QD-induced cytotoxicity in immortalised human hepatocytes and in the livers of mice. CdSe QDs induced dose-dependent cell death in hepatocytes with an IC50 = 20.4 μM. Pre-treatment with SFN (5 μM) increased cell viability in response to CdSe QDs (20 μM) from 49.5 to 89.3%. SFN induced a pro-oxidant effect characterized by depletion of intracellular reduced glutathione during short term exposure (3-6 h), followed by up-regulation of antioxidant enzymes and glutathione levels at 24 h. SFN also caused Nrf2 translocation into the nucleus, up-regulation of antioxidant enzymes and autophagy. siRNA knockdown of Nrf2 suggests that the Nrf2 pathway plays a role in the protection against CdSe QD-induced cell death. Wortmannin inhibition of SFN-induced autophagy significantly suppressed the protective effect of SFN on CdSe QD-induced cell death. Moreover, the role of autophagy in SFN protection against CdSe QD-induced cell death was confirmed using mouse embryonic fibroblasts lacking ATG5. CdSe QDs caused significant liver damage in mice, and this was decreased by SFN treatment. In conclusion, SFN attenuated the cytotoxicity of CdSe QDs in both human hepatocytes and in the mouse liver, and this protection was associated with the induction of Nrf2 pathway and autophagy.

      Item Type: Article
      Additional Information: © 2015 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
      Uncontrolled Keywords: sulforaphane;,cadmium selenide;,quantum dots;,nf-e2-related factor 2;,autophagy;,liver
      Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
      Faculty of Science > School of Pharmacy
      Faculty of Science > School of Chemistry
      Depositing User: Pure Connector
      Date Deposited: 24 Sep 2015 11:04
      Last Modified: 09 Apr 2019 11:06
      URI: https://ueaeprints.uea.ac.uk/id/eprint/54511
      DOI: 10.1371/journal.pone.0138771

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