Effect of the chelator BPCBG on the decorporation of uranium in vivo and uranium-induced damage of human renal tubular epithelial cells in vitro

This study is to assess the efficacy of BPCBG on the decorporation of uranium (Ⅵ) and protecting human renal proximal tubular epithelial cells (HK-2) against uranium-induced damage.  BPCBG at different doses was injected intramuscularly to male SD rats immediately after a single intraperitoneal injection of UO₂(CH₃COO)₂.  Twenty-four hours later uranium contents in urine, kidneys and femurs were measured by ICP-MS.  After HK-2 cells were exposed to UO₂(CH₃COO)₂ immediately or for 24 h followed by BPCBG treatment at different doses for another 24 or 48 h, the uranium contents in HK-2 cells were measured by ICP-MS, the cell survival was assayed by cell counting kit-8 assay, formation of micronuclei was determined by the cytokinesis-block (CB) micronucleus assay and the production of intracellular reactive oxygen species (ROS) was detected by 2', 7'-dichlorofluorescin diacetate (DCFH-DA) oxidation.  DTPA-CaNa₃ was used as control.  It was found that BPCBG at dosages of 60, 120, and 600 μmol·kg⁻¹ resulted in 37%−61% increase in 24 h-urinary uranium excretion, and significantly decreased the amount of uranium retention in kidney and bone to 41%−31% and 86%−42% of uranium-treated group, respectively.  After HK-2 cells that had been pre-treated with UO₂(CH₃COO)₂ for 24 h were treated with the chelators for another 24 h, 55%−60% of the intracellular uranium was removed by 10−250 μmol·L⁻¹ of BPCBG.  Treatment of uranium-treated HK-2 cells with BPCBG significantly enhanced the cell survival, decreased the formation of micronuclei and inhibited the production of intracellular ROS.  Although DTPA-CaNa₃ markedly reduced the uranium retention in kidney of rats and HK-2 cells, its efficacy of uranium removal from body was significantly lower than that of BPCBG, and it could not protect uranium-induced cell damage.  It can be concluded that BPCBG effectively decorporated the uranium from UO₂(CH₃COO)₂-treated rats and HK-2 cells, which was better than DTPA-CaNa₃.  It could also scavenge the uranium-induced intracellular ROS and protect against the uranium-induced cell damage.  BPCBG is worth further investigation.