EFFICACY OF CHELATOR CBMIDA-CaNa2 FOR THE REMOVAL OF URANIUM AND PROTECTION AGAINST URANIUM-INDUCED CELL DAMAGE IN HUMAN RENAL PROXIMAL TUBULAR CELLS

In animal experiments, catechol-3,6-bis(methyleiminodiacetic acid) (CBMIDA) was proven to be an effective chelator for the decorporation of uranium (U)(VI). In the present study, the authors investigated the molecular processes of CBMIDA-CaNa2 on the removal of U(VI) at the cellular level and explored its protective effects and mechanism against U(VI)-induced cell damage in HK-2 human renal proximal tubular cells. The results indicated that the chelating U(VI) effect of CBMIDA-CaNa2 was superior compared to that of DTPA-CaNa3; more specifically, at concentrations of 50 and 250 mu M, CBMIDA-CaNa2 can significantly reduce U(VI) uptake and increase U(VI) release in U(VI)-exposed HK-2 cells after immediate or 24-h and 48-h delayed chelator administration better than those of DTPA-CaNa3. Furthermore, CBMIDA-CaNa2 significantly decreased the lactate dehydrogenase release and the formation of micronuclei and inhibited the production of intracellular reactive oxygen species (ROS) in HK-2 cells exposed to U(VI), whereas DTPA-CaNa3 was demonstrated to be ineffective. By reviewing the results of animal experiments conducted by several other investigators, including this lab, the authors found that removal efficacy and protective effects of these two chelators for U(VI) at the cellular level agreed well with those of animal studies. In addition, although U(VI) induced the increase of metallothionein protein expression in HK-2 cells, CBMIDA-CaNa2 can mobilize and remove the U(VI) from metallothionen (MT) after 48-h delayed chelator treatment. These results suggested that CBMIDA-CaNa2 protected against U(VI)-induced HK-2 cells damaged by reducing U(VI) uptake, increasing U(VI) release and scavenging the U(VI)-induced intracellular ROS.