In vitro cytotoxicity of Cu2+, Zn2+, Ag+ and their mixtures on primary human endometrial epithelial cells

  • Jing Wu
    Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China
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  • Luyao Wang
    Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China
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  • Jing He
    Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China
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  • Changhong Zhu
    Corresponding author. Tel.: +86 027 8369 2651; fax: +86 027 83637374.
    Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China
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      To avoid the inherent disadvantages of copper-containing intrauterine device (Cu-IUD) induced by free Cu2+, two other well-performing metal ions, namely, Ag+, with long-effective antimicrobial properties, and Zn2+, as an essential trace element, are being considered for use in the future as multifunctional IUDs. The purpose of this study was to assess the cytotoxicity of these metal ions and their mixtures on primary human endometrial epithelial cells (HEECs) cultured in vitro and to provide several choices of alternative potential materials for creating excellent IUDs in the future.

      Study Design

      With the use of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-formazan (MTT-f) production, the cytotoxic effects of single metal ions (Cu2+, Zn2+, Ag+) on HEECs after exposure for 24, 48 or 72 h were investigated, and the synergistic and antagonistic effects of two ions applied simultaneously were also assessed.


      The cytotoxicity of the metal ions on HEECs ranked as follows: Ag+>Cu2+>Zn2+. All combinations of those tested indicated that the Cu2++Zn2+ system exhibited an antagonistic effect absolutely, the Zn2++Ag+ system showed both antagonism and slight synergism, and asynergistic effect was observed in the Cu2++Ag+ system.


      From a perspective of favorable biocompatibility, Zn2+ and the Cu2++Zn2+ mixture showed evidence of potential components for use in future IUDs. Although having strong cytotoxicity, Ag+ with its low release rate and broad-spectrum antibiotic activity may also be considered. The study also demonstrated the relative stability of Cu2+ as a classic material of IUD.


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