title: [Effect of the chelator BPCBG on the decorporation of uranium in vivo and uranium-induced damage of human renal tubular epithelial cells in vitro].
abstract: 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 micromol 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 micromol 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.
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
authors.forename: Yi-zhong
authors.initials: YZ
authors.lastname: Bao
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Yu-xing
authors.initials: YX
authors.lastname: Hu
authors.forename: Ai-hong
authors.initials: AH
authors.lastname: Xu
authors.forename: Mei-zhen
authors.initials: MZ
authors.lastname: Sun
authors.forename: Hong-hong
authors.initials: HH
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002614:Chelating Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology; D008297:Male; D015162:Micronucleus Tests; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014501:Uranium / Q000378:metabolism* / Q000652:urine
chemical_list: D002614:Chelating Agents; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; C005460:uranyl acetate; D014501:Uranium