The chelator BPCBG decorporates uranium and protects against uranium-induced kidney injury in rats / 中华放射医学与防护杂志

ABSTRACT

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.