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Abstract: SA-PO589

Ceria-Zirconia Nanoparticles as an Enhanced Multi-Antioxidant Attenuates Apoptosis of Human Kidney Proximal Tubular Epithelial Cells in Hypoxia

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Yoon, Se-Hee, Konyang University Hospital, Daejeon, Korea (the Republic of)
  • Cho, Jang-Hee, Kyungpook National University Hospital, Daegu, Korea (the Republic of)
  • Hwang, Won Min, Konyang University Hospital, Daejeon, Korea (the Republic of)
  • Yun, Sung-Ro, Konyang University Hospital, Daejeon, Korea (the Republic of)
  • Yoon, Kuk-Ro, Hannam University, Daejeon, Korea (the Republic of)
Background

Hypoxia is an important cause of acute kidney injury (AKI) in various conditions because kidneys are one of the most susceptible organ to hypoxia. Various mechanisms have been introduced as mediators of the AKI caused by hypoxia, including calcium overload, endoplasmic reticulum stress, complement system activation, and reactive oxygen species (ROS). ROS play an important role in hypoxia induced AKI by affecting the function of cellular DNA, proteins, and lipids. The use of antioxidants can benefit the control and prevention of hypoxia induced AKI. Ceria-Zirconia nanoparticles (CZ NPs) exhibit superoxide dismutase and catalase mimetic activities. We investigated the effect of CZ NPs in cultures of hypoxia exposed human proximal tubular epithelial cells.

Methods

CZ NPs with size 2-3nm were synthesized using non-hydrolytic sol-gel reaction. To investigate the catalytic effect of CZ NPs, reactive oxygen species (ROS) production was measured using DHE, DCF-DA and amplex red assay. Cellular survival rate and cytotoxicity were measured with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cellular signaling pathway were studied by real time polymerase chain reaction and Western blot analysis.

Results

Cell survival was reduced in a dose-dependent manner for 24h after hypoxia exposure. Hypoxia caused a significant increase in ROS production 24 h after hypoxia. The extent of the effect of hypoxia on ROS levels was significantly reduced by CZ NPs treatment. CZ NPs downregulated proinflammatory markers and reduced caspase 3/7 activity in hypoxic HK-2 cells. CZ NPs also improved the survival of HK-2 cells in response to hypoxia.

Conclusion

CZ NPs have the potential as a therapeutic medicine for preventing ROS-related hypoxia induced AKI