Limits...
Sulforaphane Protects the Liver against CdSe Quantum Dot-Induced Cytotoxicity.

Wang W, He Y, Yu G, Li B, Sexton DW, Wileman T, Roberts AA, Hamilton CJ, Liu R, Chao Y, Shan Y, Bao Y - PLoS ONE (2015)

Bottom Line: Wortmannin inhibition of SFN-induced autophagy significantly suppressed the protective effect of SFN on CdSe QD-induced cell death.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.

View Article: PubMed Central - PubMed

Affiliation: Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus

The protective effect of SFN against the hepatoxicity of CdSe QDs in mouse liver.Liver toxicity in mice was evaluated by histological examination after H&E staining. CdSe QDs caused hepatocellular necrosis with cell swelling and modulated nuclear morphology as indicated by the arrow. The original magnification was 400X.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4581733&req=5

pone.0138771.g007: The protective effect of SFN against the hepatoxicity of CdSe QDs in mouse liver.Liver toxicity in mice was evaluated by histological examination after H&E staining. CdSe QDs caused hepatocellular necrosis with cell swelling and modulated nuclear morphology as indicated by the arrow. The original magnification was 400X.

Mentions: Liver toxicity in mice was evaluated by histological examination after H&E staining (Fig 7). In the control group, the hepatocytes were arranged in regular rows of hepatic cords; there was no hepatic sinusoid congestion nor were there any abnormal changes in liver cells (Fig 7-a). However, in the group exposed to CdSe QDs, hepatocellular ballooning degeneration occurred over large areas (Fig 7-b). Many hepatocytes have diffusion in cytoplasm and look less nucleated possibly because of nuclear condensation, break up and loss (pyknosis, karyorrhexis and karyolysis). If this state continues to develop, it would lead to hepatocellular necrosis. Interestingly and as predicted, the SFN-protected group incurred almost no cell death and the liver histology was similar to that of control groups (Fig 7-c).


Sulforaphane Protects the Liver against CdSe Quantum Dot-Induced Cytotoxicity.

Wang W, He Y, Yu G, Li B, Sexton DW, Wileman T, Roberts AA, Hamilton CJ, Liu R, Chao Y, Shan Y, Bao Y - PLoS ONE (2015)

The protective effect of SFN against the hepatoxicity of CdSe QDs in mouse liver.Liver toxicity in mice was evaluated by histological examination after H&E staining. CdSe QDs caused hepatocellular necrosis with cell swelling and modulated nuclear morphology as indicated by the arrow. The original magnification was 400X.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581733&req=5

pone.0138771.g007: The protective effect of SFN against the hepatoxicity of CdSe QDs in mouse liver.Liver toxicity in mice was evaluated by histological examination after H&E staining. CdSe QDs caused hepatocellular necrosis with cell swelling and modulated nuclear morphology as indicated by the arrow. The original magnification was 400X.
Mentions: Liver toxicity in mice was evaluated by histological examination after H&E staining (Fig 7). In the control group, the hepatocytes were arranged in regular rows of hepatic cords; there was no hepatic sinusoid congestion nor were there any abnormal changes in liver cells (Fig 7-a). However, in the group exposed to CdSe QDs, hepatocellular ballooning degeneration occurred over large areas (Fig 7-b). Many hepatocytes have diffusion in cytoplasm and look less nucleated possibly because of nuclear condensation, break up and loss (pyknosis, karyorrhexis and karyolysis). If this state continues to develop, it would lead to hepatocellular necrosis. Interestingly and as predicted, the SFN-protected group incurred almost no cell death and the liver histology was similar to that of control groups (Fig 7-c).

Bottom Line: Wortmannin inhibition of SFN-induced autophagy significantly suppressed the protective effect of SFN on CdSe QD-induced cell death.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.

View Article: PubMed Central - PubMed

Affiliation: Norwich Medical School, University of East Anglia, Norwich, Norfolk, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus