title: In vitro cytotoxicity of Cu²⁺, Zn²⁺, Ag⁺ and their mixtures on primary human endometrial epithelial cells.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Luyao
authors.initials: L
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.forename: Changhong
authors.initials: C
authors.lastname: Zhu
mesh_terms: D000328:Adult; D002412:Cations / Q000009:adverse effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003300:Copper / Q000009:adverse effects*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D004867:Equipment Design / Q000379:methods; D005260:Female; D006801:Humans; D007436:Intrauterine Devices, Medicated / Q000009:adverse effects; D008856:Microscopy, Fluorescence; D009994:Osmolar Concentration; D012834:Silver / Q000009:adverse effects*; D013997:Time Factors; D015032:Zinc / Q000009:adverse effects*
chemical_list: D002412:Cations; D012834:Silver; D003300:Copper; D015032:Zinc