RESUMO
Objective To explore the dose- and time-responses of BPCBG on the decorporation of uranium and its protective effects for uranium-induced kidney injury in rats. Methods Sprague-Dawley (SD) male rats were randomly divided into 4 -7 groups:normal control group,uranium poisoning group,different doses of BPCBG groups and DTPA-CaNa3 group. Rats in chelating agents-treated groups were either injected intramuscularly with 60,120 and 600 μmol/kg of BPCBG or 120 and 600 μmol/kg of DTPA-CaNa3 immediately after intraperitoneal injection of uranyl acetate dihydrate,or injected with 120 μmol/kg of BPCBG 0.5,2 h before or 0,0.5,1 and 2 h after injection of uranium. Uranium poisoning group rats were injected with normal saline after intraperitoneal injection of uranyl acetate dihydrate,and the normal control group rats were merely injected with normal saline. The uranium content in urine,kidney and femurs were detected 24 h after chelator injections by ICP-MS method.After injecting a dose of 500 μg uranyl acetate dihydrate,rats were injected with 600 μmol/kg of BPCBG or 1200 μmol/kg of DTPA-CaNa3. Histopathological changes in the kidney and serum creatinine and urea nitrogen were examined 48 h after chelator administration.Results Prompt injections of BPCBG resulted in 37％ -61％ ( t =2.22,4.43,5.80,P ＜ 0.05 ) increase in 24 h-urinary uranium excretion,and significantly decreased the levels of uranium in kidney and bone by 59％ -69％ (t=3.33,5-59,4-53,P＜0.01) and 14％ -58％ (t =2.15,8.70,9.10,P ＜ 0.05 ) respectively in a dose-dependent manner. BPCRG injection obviously reduced the severity of the uranium-induced histological alterations in the kidney,which was in parallel with the amelioration noted in serum indicators,serum creatinine and urea nitrogen,of uranium nephrotoxicity.Advanced 0.5 h or delayed 0.5 and 1 h administrations of BPCBG were effective in 24 h-urinary uranium excretion ( advanced 0.5 h:t =4.34,delayed 0.5 h:t =3.35,P ＜ 0.05 ),decreasing accumulation of kidney uranium ( t =5.75,7.74,5.87,P ＜ 0.05 ) and accumulation of hone uranium (t =6.43,5.222,2.60,P ＜0.05),but the efficacy decreased with the interval time between uranium and BPCBG injection. Although DTPA-CaNa3 markedly reduced uranium retention in kidney (120,600 μmol/kg,t =2.28,3.35,P ＜ 0.05 ),its efficacy in uranium removal was significantly lower than that of BPCBG,and it had no protective effects against uranium-induced nephrotoxicity.Conclusions BPCBG can effectively decorporate uranium from rats and protect against uranium-induced kidney injury of rats.
RESUMO
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.