In vitro cytogenetic analysis of two different anti-phosphates (sevelamer hydrochloride and calcium carbonate) agents used by patients with hyperphosphatemia


Ulaya G., İLA H. B.

DRUG AND CHEMICAL TOXICOLOGY, cilt.46, sa.4, ss.699-707, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 46 Sayı: 4
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1080/01480545.2022.2083150
  • Dergi Adı: DRUG AND CHEMICAL TOXICOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.699-707
  • Anahtar Kelimeler: Anti-phosphate, sevelamer hydrochloride, calcium carbonate, micronucleus test, comet assay, Ames test, genotoxicity
  • Çukurova Üniversitesi Adresli: Evet

Özet

Sevelamer hydrochloride (SH) and calcium carbonate (CaCO3) are two agents included in the phosphate-binding group which are frequently prescribed in the treatment of patients with hyperphosphatemia. However, there are no satisfactory studies on the genotoxic effects of SH in vitro. This study was conducted to reveal the genotoxic and/or cytotoxic potential of these two drugs in cultured human peripheral lymphocytes. Human peripheral lymphocytes were treated with SH and CaCO3 at sublethal concentrations for 24 or 48 h for micronucleus assay and 1 h in the comet assay. CaCO3 and SH stimulated a slight increase in micronucleus formation however this increase was not significant compared to the control group. According to the findings of the comet test, only one concentration of the SH caused significant DNA damage (2 mg/ml, 48 h) whereas CaCO3 did not cause important DNA breakage. No significant oxidative damage or anti-radical effect caused by test substances was observed on the pure pBR322 plasmid DNA in a cell-free medium. Also, it was found that the drugs were devoid of mutagenic activity in the Ames test, but had a weak cytotoxic effect. Both test substances, particularly SH, significantly reduced the nuclear division index compared to the control group. In conclusion, the cytotoxic effect of SH was evident on the basis of in vitro tests and slightly higher than CaCO3.