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Toxicologic Pathology
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Articles

Temporal Clinical Chemistry and Microscopic Renal Effects Following Acute Uranyl Acetate Exposure

Kurt L. Zimmerman1, David S. Barber2, Marion F. Ehrich1, Lynette Tobias1, Sandra Hancock1, J. Hinckley1, Ellen M. Binder1 and Bernard S. Jortner1

1 Laboratory for Neurotoxicity Studies, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA
2 Department of Physiological Sciences, Center for Environmental and Human Toxicology, Gainesville, FL, USA

Correspondence: Address correspondence to Kurt L. Zimmerman, Laboratory for Neurotoxicity Studies, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061-0002. E-mail:kzim-merm{at}vt.edu

Military use of depleted uranium (DU) has renewed interest in the toxicology of this metal. In this study, the nephrotoxicity of single exposure DU was assessed with and without pre-exposure stress. Adult male Sprague–Dawley rats (n = 288) were administered a single IM dose of 0, 0.1, 0.3 or 1.0 mg/kg DU. Corticosterone concentrations (ng/ml, mean ± SD) were 763.65 ± 130.94 and 189.80 ± 90.81 for swim stressed and unstressed rats. Serum and kidney uranium concentration, hematocrit, chemistry, and renal histology were assessed on sacrifice days 1, 3, 7 and 30 post-DU-dosing. Dose related increases in serum and kidney uranium were noted. DU concentration peaked day 1 in the kidney and days 3–7, in the serum. Dose-related elevations of Cr and BUN concentrations were seen on days 3 and 7. A decline in serum albumin coincided with Cr and BUN suggesting protein losing nephropathy. Dose related acute tubular necrosis and proliferative glomulonephritis were seen. Tubular regeneration in low dose rats was almost complete by day 30. High dose rats had extensive tubular necrosis and delayed regeneration with focal residual chronic interstitial nephritis and cortical scarring. Glomular changes were reversed in all treatment groups by day 30. Stress exposure had no impact on any measured renal parameter.

Key Words: Clinical chemistry • microscopic • renal uranyl acetate

Abbreviations: Alb, albumin • ALP, alkaline phosphatase • ALT, alanine aminotransferase • BUN, blood urea nitrogen • Ca++, calcium • Cl–, chloride • Cr, serum creatinine • Cr, creatinine • DU, depleted uranium • EM, electron microscopy • Glb, globulin • Glu, glucose • IM, intramuscular • K+, potassium • Na+, serum sodium • TCO2, carbon dioxide • P, phosphorus • TBil, total bilirubin • TP, total protein

Toxicologic Pathology, Vol. 35, No. 7, 1000-1009 (2007)
DOI: 10.1080/01926230701748446
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