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Immunotoxicity of zinc oxide nanoparticles with different size and electrostatic charge.

Kim CS, Nguyen HD, Ignacio RM, Kim JH, Cho HC, Maeng EH, Kim YR, Kim MK, Park BK, Kim SK - Int J Nanomedicine (2014)

Bottom Line: We found that in a cell viability assay, ZnO NPs with different size and charge could induce differential cytotoxicity to Raw 264.7 cells.The CD4(+)/CD8(+) ratio, a marker for matured T-cells was slightly reduced, which implies the alteration of immune status induced by ZnO NPs.Consistently, serum levels of pro/anti-inflammatory (interleukin [IL]-1β, tumor necrosis factor-α, and IL-10) and T helper-1 cytokines (interferon-γ and IL-12p70) in ZnO NP-fed mice were significantly suppressed.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea.

ABSTRACT
While zinc oxide (ZnO) nanoparticles (NPs) have been recognized to have promising applications in biomedicine, their immunotoxicity has been inconsistent and even contradictory. To address this issue, we investigated whether ZnO NPs with different size (20 or 100 nm) and electrostatic charge (positive or negative) would cause immunotoxicity in vitro and in vivo, and explored their underlying molecular mechanism. Using Raw 264.7 cell line, we examined the immunotoxicity mechanism of ZnO NPs as cell viability. We found that in a cell viability assay, ZnO NPs with different size and charge could induce differential cytotoxicity to Raw 264.7 cells. Specifically, the positively charged ZnO NPs exerted higher cytotoxicity than the negatively charged ones. Next, to gauge systemic immunotoxicity, we assessed immune responses of C57BL/6 mice after oral administration of 750 mg/kg/day dose of ZnO NPs for 2 weeks. In parallel, ZnO NPs did not alter the cell-mediated immune response in mice but suppressed innate immunity such as natural killer cell activity. The CD4(+)/CD8(+) ratio, a marker for matured T-cells was slightly reduced, which implies the alteration of immune status induced by ZnO NPs. Accordingly, nitric oxide production from splenocyte culture supernatant in ZnO NP-fed mice was lower than control. Consistently, serum levels of pro/anti-inflammatory (interleukin [IL]-1β, tumor necrosis factor-α, and IL-10) and T helper-1 cytokines (interferon-γ and IL-12p70) in ZnO NP-fed mice were significantly suppressed. Collectively, our results indicate that different sized and charged ZnO NPs would cause in vitro and in vivo immunotoxicity, of which nature is an immunosuppression.

No MeSH data available.


Related in: MedlinePlus

Detection of NO induced by ZnO NPs on mouse splenocytes. Splenocytes were isolated and cultured. NO production in the supernatant was measured by the Griess reaction.Notes: Values are presented as mean ± SEM, n=5. **P<0.01, and ***P<0.001. AE = American Elements (Los Angeles, CA, USA); SM = Sumitomo Osaka Cement Co, Ltd, (Tokyo, Japan).Abbreviations: NC, normal control; NO, nitric oxide; NP, nanoparticle; SEM, standard error of the mean; ZnO, zinc oxide.
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f4-ijn-9-195: Detection of NO induced by ZnO NPs on mouse splenocytes. Splenocytes were isolated and cultured. NO production in the supernatant was measured by the Griess reaction.Notes: Values are presented as mean ± SEM, n=5. **P<0.01, and ***P<0.001. AE = American Elements (Los Angeles, CA, USA); SM = Sumitomo Osaka Cement Co, Ltd, (Tokyo, Japan).Abbreviations: NC, normal control; NO, nitric oxide; NP, nanoparticle; SEM, standard error of the mean; ZnO, zinc oxide.

Mentions: NO is a reactive form of nitrogen and is an important cellular signaling molecule involved in several biological processes, and moreover, serves as one of the key mediators of immune defense. To further explore the impact of ZnO NPs on immune defense, we measured the level of splenic NO production after 14 days treatment. As shown in Figure 4, a significant decrease in NO level occurred after administration of ZnOSM20(−) and ZnOAE100(+/−). However, there was no substantial difference of NO level in ZnOSM20(+)-fed mice as compared with the control.


Immunotoxicity of zinc oxide nanoparticles with different size and electrostatic charge.

Kim CS, Nguyen HD, Ignacio RM, Kim JH, Cho HC, Maeng EH, Kim YR, Kim MK, Park BK, Kim SK - Int J Nanomedicine (2014)

Detection of NO induced by ZnO NPs on mouse splenocytes. Splenocytes were isolated and cultured. NO production in the supernatant was measured by the Griess reaction.Notes: Values are presented as mean ± SEM, n=5. **P<0.01, and ***P<0.001. AE = American Elements (Los Angeles, CA, USA); SM = Sumitomo Osaka Cement Co, Ltd, (Tokyo, Japan).Abbreviations: NC, normal control; NO, nitric oxide; NP, nanoparticle; SEM, standard error of the mean; ZnO, zinc oxide.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4279726&req=5

f4-ijn-9-195: Detection of NO induced by ZnO NPs on mouse splenocytes. Splenocytes were isolated and cultured. NO production in the supernatant was measured by the Griess reaction.Notes: Values are presented as mean ± SEM, n=5. **P<0.01, and ***P<0.001. AE = American Elements (Los Angeles, CA, USA); SM = Sumitomo Osaka Cement Co, Ltd, (Tokyo, Japan).Abbreviations: NC, normal control; NO, nitric oxide; NP, nanoparticle; SEM, standard error of the mean; ZnO, zinc oxide.
Mentions: NO is a reactive form of nitrogen and is an important cellular signaling molecule involved in several biological processes, and moreover, serves as one of the key mediators of immune defense. To further explore the impact of ZnO NPs on immune defense, we measured the level of splenic NO production after 14 days treatment. As shown in Figure 4, a significant decrease in NO level occurred after administration of ZnOSM20(−) and ZnOAE100(+/−). However, there was no substantial difference of NO level in ZnOSM20(+)-fed mice as compared with the control.

Bottom Line: We found that in a cell viability assay, ZnO NPs with different size and charge could induce differential cytotoxicity to Raw 264.7 cells.The CD4(+)/CD8(+) ratio, a marker for matured T-cells was slightly reduced, which implies the alteration of immune status induced by ZnO NPs.Consistently, serum levels of pro/anti-inflammatory (interleukin [IL]-1β, tumor necrosis factor-α, and IL-10) and T helper-1 cytokines (interferon-γ and IL-12p70) in ZnO NP-fed mice were significantly suppressed.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon-do, Republic of Korea.

ABSTRACT
While zinc oxide (ZnO) nanoparticles (NPs) have been recognized to have promising applications in biomedicine, their immunotoxicity has been inconsistent and even contradictory. To address this issue, we investigated whether ZnO NPs with different size (20 or 100 nm) and electrostatic charge (positive or negative) would cause immunotoxicity in vitro and in vivo, and explored their underlying molecular mechanism. Using Raw 264.7 cell line, we examined the immunotoxicity mechanism of ZnO NPs as cell viability. We found that in a cell viability assay, ZnO NPs with different size and charge could induce differential cytotoxicity to Raw 264.7 cells. Specifically, the positively charged ZnO NPs exerted higher cytotoxicity than the negatively charged ones. Next, to gauge systemic immunotoxicity, we assessed immune responses of C57BL/6 mice after oral administration of 750 mg/kg/day dose of ZnO NPs for 2 weeks. In parallel, ZnO NPs did not alter the cell-mediated immune response in mice but suppressed innate immunity such as natural killer cell activity. The CD4(+)/CD8(+) ratio, a marker for matured T-cells was slightly reduced, which implies the alteration of immune status induced by ZnO NPs. Accordingly, nitric oxide production from splenocyte culture supernatant in ZnO NP-fed mice was lower than control. Consistently, serum levels of pro/anti-inflammatory (interleukin [IL]-1β, tumor necrosis factor-α, and IL-10) and T helper-1 cytokines (interferon-γ and IL-12p70) in ZnO NP-fed mice were significantly suppressed. Collectively, our results indicate that different sized and charged ZnO NPs would cause in vitro and in vivo immunotoxicity, of which nature is an immunosuppression.

No MeSH data available.


Related in: MedlinePlus