title: Sulforaphane Protects the Liver against CdSe Quantum Dot-Induced Cytotoxicity.
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.
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin, Heilongjiang, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors.forename: Guodong
authors.initials: G
authors.lastname: Yu
authors.affiliation: Center of Safety Evaluation of Drugs, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, P. R. China.
authors.forename: Baolong
authors.initials: B
authors.lastname: Li
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors.forename: Darren W
authors.initials: DW
authors.lastname: Sexton
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wileman
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors.forename: Alexandra A
authors.initials: AA
authors.lastname: Roberts
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Hamilton
authors.affiliation: School of Chemistry, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors.forename: Ruoxi
authors.initials: R
authors.lastname: Liu
authors.affiliation: School of Chemistry, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Chao
authors.affiliation: School of Food Science and Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, P. R. China.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Shan
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Bao
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D019187:Cadmium Compounds / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D055785:Gene Knockdown Techniques; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D000072019:Kelch-Like ECH-Associated Protein 1; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D008813:Mice, Inbred ICR; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D045663:Quantum Dots / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018036:Selenium Compounds / Q000633:toxicity*; D013454:Sulfoxides; D014158:Transcription, Genetic / Q000187:drug effects; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D019187:Cadmium Compounds; D047908:Intracellular Signaling Peptides and Proteins; D017879:Isothiocyanates; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D020011:Protective Agents; D012333:RNA, Messenger; D018036:Selenium Compounds; D013454:Sulfoxides; C025946:3-methyladenine; D008668:Metallothionein; C058667:cadmium selenide; C016766:sulforaphane; D005978:Glutathione; D000225:Adenine; D000077191:Wortmannin