Comparative in vitro cytogenetic analysis of calcium carbonate and sevelamer hydrochloride agents used by patients with hyperphosphatemia

This study was conducted to compare the genotoxic and / or cytotoxic potential of two agents included in the phosphate binding group, Sevelamer hydrochloride and Calcium carbonate, which are frequently prescribed in the treatment of patients with hyperphosphatemia. Micronucleus (MN) and single cell gel electrophoresis (comet assay) tests were performed on human peripheral lymphocytes. In addition, the Ames Salmonella/microsome mutagenicity assay was performed with mutant strains of Salmonella typhimurium (TA98 and TA100) to determine whether they stimulate substitutions and frame shift mutations. Human peripheral lymphocytes were treated with sevelamer hydrochloride and calcium carbonate at concentrations of 1/2, 1, and 2 mg / mL for 20 and 44 hours for micronucleus assay and 1 hour in the comet assay. In the Ames / Salmonella bacterial reverse mutation test, sevelamer hydrochloride and calcium carbonate concentrations of 2 mg / mL, 1 mg / mL, 0.5 mg / mL, 0.25 mg / mL and 0.125 mg / mL were used. In this study, sevelamer hydrochloride and calcium carbonate stimulated slight increase in micronucleus formation but this increase was not significant compared to the results of the control group. According to the findings of the comet test, sevelamer hydrochloride and calcium carbonate did not cause significant DNA damage with one exception (2 mg / mL, sevelamer hydrochloride, 48 hours). In the Ames test, it was found that the drugs were devoid of mutagenic activity in bacterial assay, but had a weak cytotoxic effect. Both sevelamer hydrochloride and calcium carbonate, particularly SH, significantly reduced NBI compared to the control group. Thus, a weak cytotoxicity effect can be mentioned. Furthermore, sevelamer hydrochloride was more reactive in terms of genotoxicity and cytotoxicity than calcium carbonate when the two agents were compared. Key Words: Sevelamer Hydrochloride, Calcium Carbonate, Micronucleus, Single Cell Gel Electrophoresis, Ames Salmonella/microsome mutagenicity assay.