Effect of DTPA on the nephrotoxicity induced by uranium in the rat.
The only treatment proposed after human contamination with MOX (mixed oxide of uranium and plutonium) is diethylenetriaminepentaacetic acid (DTPA), because plutonium is considered to be the major risk. However, both DTPA and uranium are nephrotoxic at high dosages and DTPA has been shown to increase in vitro the cytotoxicity induced by uranium on cultured epithelial tubular cells. This work aimed to test this effect in vivo. Rats were injected with subtoxic (57 microg kg(-1)) to toxic (639 microg kg(-1)) amounts of uranium as nitrate at 0 h, they received two DTPA injections (30 micromol kg(-1)) at 2 min and 24 h and were euthanased at 48 h. The nephrotoxic effects were evaluated by measurement of the body weight gain, food and water intake, measurement of biochemical parameters in urine and blood, and histological examination of one kidney. The main result was that DTPA did not increase the nephrotoxicity induced by uranium in the range of concentrations tested, which was inconsistent with the in vitro results.
Houpert
P
P
Institut de Radioprotection et de Sûreté Nucléaire, Département de Protection de la Santé de l'Homme et de Dosimétrie, Service de Dosimétrie, BP no166, F 26702 Pierrelatte Cedex, France. pascale.houpert@irsn.fr
Muller
D
D
Chazel
V
V
Claraz
M
M
Paquet
F
F
D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects; D015913:Chelation Therapy / Q000379:methods*; D003666:Decontamination / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004357:Drug Synergism; D004848:Epithelium / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D008297:Male; D009401:Nephrosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D004369:Pentetic Acid / Q000008:administration & dosage* / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D014501:Uranium / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity*
D002614:Chelating Agents; D014501:Uranium; D004369:Pentetic Acid