Comparative effects of the chelators sodium 4,5-dihydroxybenzene-1,3-disulfonate (Tiron) and diethylenetriaminepentaacetic acid (DTPA) on acute uranium nephrotoxicity in rats.
Sodium 4,5-dihydroxybenzene-1,3-disulfonate (Tiron) and diethylenetriaminepentaacetic acid (DTPA) are two chelating agents that have been demonstrated to be effective in the treatment of experimental poisoning by a number of heavy metals. In this study, the effects of Tiron and DTPA on uranium-induced nephrotoxicity were evaluated in a rat model. A series of four Tiron or DTPA injections was administered intraperitoneally to adult male Sprague-Dawley rats immediately after a single subcutaneous injection of uranyl acetate dihydrate (5 mg/kg) and at 24, 48 and 72 h thereafter. Positive and negative control groups received 0.9% saline with or without uranyl acetate, respectively. Tiron effectiveness was assessed at 400, 800 and 1600 mg/kg, whereas DTPA was administered at 250, 500 and 1000 mg/kg. Although the urinary excretion of uranium was significantly enhanced by Tiron administration, significant amounts of uranium still remained in the kidney at the end of the treatment. However, the partial reduction of the renal uranium concentrations was in accordance with the amelioration noted in some urinary and serum indicators of uranium nephrotoxicity. Moreover, Tiron administration also reduced the severity of the uranium-induced histological alterations in the kidney. According to these results, Tiron offers only a modest encouragement with regard to its possible therapeutic potential to treat acute uranium-induced nephrotoxic effects. In turn, DTPA was less effective than Tiron in protecting against the nephrotoxicity of uranium in rats.
Domingo
J L
JL
Laboratory of Toxicology and Environmental Health, School of Medicine, Rovira i Virgilt University, Reus, Spain.
de la Torre
A
A
Bellés
M
M
Mayayo
E
E
Llobet
J M
JM
Corbella
J
J
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003404:Creatinine / Q000378:metabolism / Q000652:urine; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009942:Organometallic Compounds / Q000633:toxicity*; D004369:Pentetic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011041:Poisoning / Q000517:prevention & control; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D014501:Uranium / Q000008:administration & dosage / Q000633:toxicity* / Q000652:urine; D014508:Urea / Q000652:urine
D002614:Chelating Agents; D009942:Organometallic Compounds; C005460:uranyl acetate; D014501:Uranium; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D004369:Pentetic Acid; D014508:Urea; D003404:Creatinine; D000118:Acetylglucosaminidase