Clinical diagnostic indicators of renal and bone damage in rats intramuscularly injected with depleted uranium.
The toxic effects and changes in biochemical markers related to kidney and bone in depleted uranium (DU)-injected rats were examined in order to clarify the relation between clinical biochemical markers and the degree of damage in these organs. Male Wistar rats received a single injection in the femoral muscles of 0.2, 1.0 or 2.0 mg kg(-1) of DU which was dissolved in nitric acid solution adjusted to pH 3.2, for comparison with the group injected with nitric acid solution, and the control group. Urine and faeces were collected periodically over a 24 h period. Thereafter, the rats were killed at 28 d after DU injection. The body weights of the DU-injected groups decreased dose-dependently for the first 3-7 d, and then began to increase. The DU concentrations in the urine and faeces decreased rapidly within 3-7 d after DU injection. Urinary N-acetyl-beta-D-glucosaminidase (NAG)/creatinine peaked at the third day after DU injection, with a high correlation to the injected DU doses. There were high correlations among the injected DU doses, DU concentrations in the kidney and urinary NAG/creatinine values that were obtained at 28 d, respectively. The blood urea nitrogen (BUN) and creatinine in the serum also showed a high correlation with the DU-injected doses. The results indicated that urinary NAG/creatinine, BUN and creatinine in serum were useful indicators to diagnose the renal damage by DU, as well as to estimate the DU intake and concentration in the kidney when the intake is >2 mg kg(-1) DU. The total bone mineral density of the proximal metaphysis of the tibia decreased in the 2 mg kg(-1) DU group. In addition, alterations of the trabecular bone structure by inhibiting bone formation and promoting bone resorption were observed by bone histomorphometery. The bone biochemical markers osteocalcin, tartrate-resistance acid phosphatase, pyridinoline and rat-parathyroid hormone increased in all the DU injected groups, indicating that these markers were useful as sensitive indicators for diagnosing bone damage, even if the DU dose injected is low.
Fukuda
S
S
Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, 4-9-1, Anagawa, Inege-ku, Chiba 263-8555, Japan. s_fukuda@nirs.go.jp
Ikeda
M
M
Chiba
M
M
Kaneko
K
K
D000818:Animals; D001847:Bone Diseases / Q000209:etiology* / Q000473:pathology*; D004307:Dose-Response Relationship, Radiation; D007220:Industrial Waste / Q000009:adverse effects; D007273:Injections, Intramuscular / Q000009:adverse effects; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology*; D008297:Male; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D014501:Uranium / Q000633:toxicity*
D007220:Industrial Waste; D014501:Uranium