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Clinical diagnostic indicators of renal and bone damage in rats intramuscularly injected with depleted uranium
1Research 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
Abstract:
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.
Insights
Depleted uranium (DU) exposure causes kidney and bone damage in rats. Urinary N-acetyl-beta-D-glucosaminidase (NAG)/creatinine, blood urea nitrogen (BUN), and serum creatinine effectively indicate kidney damage and DU intake.
Area of Science:
- Toxicology
- Biochemistry
- Radiological Health
Background:
- Depleted uranium (DU) exposure poses risks to human health, particularly affecting kidney and bone tissues.
- Understanding the relationship between DU exposure levels and resulting biochemical changes is crucial for accurate diagnosis and risk assessment.
Purpose of the Study:
- To investigate the toxic effects of depleted uranium (DU) on kidney and bone health in rats.
- To correlate clinical biochemical markers with the extent of organ damage following DU exposure.
- To evaluate the utility of specific biomarkers for diagnosing DU-induced renal and bone damage.
Main Methods:
- Male Wistar rats were injected with varying doses of DU (0.2, 1.0, 2.0 mg kg(-1)) or a control solution.
- Urine and feces were collected over 24 hours; rats were sacrificed at 28 days post-injection.
- Biochemical markers in urine and serum (e.g., NAG/creatinine, BUN, creatinine) and bone parameters (e.g., bone mineral density, histomorphometry, bone markers) were analyzed.
Main Results:
- DU exposure led to a dose-dependent decrease in body weight initially, followed by recovery.
- Urinary NAG/creatinine, serum BUN, and creatinine levels correlated significantly with injected DU doses and kidney DU concentrations.
- Bone mineral density decreased, and bone histomorphometry revealed inhibited formation and increased resorption. Bone markers (osteocalcin, TRAP, pyridinoline, PTH) increased, indicating sensitivity to DU exposure.
Conclusions:
- Urinary NAG/creatinine, serum BUN, and creatinine are reliable indicators of DU-induced renal damage and can estimate DU intake (>2 mg kg(-1)).
- Bone biochemical markers are sensitive indicators for diagnosing bone damage from even low DU doses.
- These findings aid in diagnosing and assessing the extent of organ damage caused by depleted uranium exposure.

