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Effect of Diethylenetriaminepentaacetate (DTPA) on the nephrotoxicity induced by uranium in the rat.

Workshop on Internal Dosimetry of Radionuclides - Occupational, Public and Medical Exposure - 9-12 September 2002 - New College, Oxford, United Kingdom P. Houpert, D. Müller, V. Chazel, M. Donnadieu-Claraz, F. Paquet

Summary

The only treatment proposed after an accidental contamination of workers with MOX (Mixed Oxide of uranium and plutonium) is DTPA, because plutonium is considered to be the major risk after a MOX contamination. But DTPA and uranium are both nephrotoxic at high dosages, and their joint effects on the kidney are unknown. We have previously shown that in vitro DTPA increased the cytotoxicity induced by uranium on cultured epithelial tubular cells (LLC-PK1). This work aimed to test this effect in vivo. Sprague Dawley rats were injected intraperitoneally with subtoxic to toxic amounts of uranium nitrate (57 to 639 µg.kg-1 BW). They received a Na3CaDTPA injection (30 µmol.kg-1) 2 min later and a Na3ZnDTPA injection (30 µmol.kg-1) 24 h later. They were euthanatized 24 h after the last injection. The body weight gain, food and water intake were measured daily. The nephrotoxic effects were evaluated by measurement of the urea, creatinine, glucose and protein levels in urine, the urea, creatinine, glucose, ALT, AST and gammaGT levels in blood and by histological examination of the right kidney. The uranium levels were measured in urine, faeces and tissues. The main result was that DTPA did not increase the nephrotoxicity induced by uranium in the range of 57 to 639 µg U.kg-1, which was inconsistent with the in vitro results. Concerning uranium nephrotoxicity, we observed that the glomerular filtration was impaired at 147 µg U.kg-1, although the functional or structural tubular injuries were induced at 659 µg U.kg-1.

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