Narrow Results

Effects of one human-dose (30 µmol/kg) of calcium salt of diethylenetriaminepentaacetic acid (Ca-DTPA) on the urinary excretion of essential metals and on their concentration in several tissues were studied in rats by particle induced X-ray emission (PIXE). Ca-DTPA enhanced the urinary excretion of manganese, iron, copper and zinc, while their concentration in the liver, kidneys, brain and thigh bone remained unchanged. These results suggest that urinary loss of these metals caused by Ca-DTPA can be compensated by homeostatic mechanisms in the body under the treatment schedule of one human-dose per day.

Zn-DTPA was injected intraperitoneally into rats (30 µmol/kg) with a single dose or a daily dose for 10 consecutive days. Urine samples were collected for 24 hours after the single injection and tissue samples were excised 20 hours after the final of the consecutive injections. Elements in these samples were analyzed by PIXE. Zn-DTPA raised the urinary concentration of zinc and copper, and their urinary losses caused by Zn-DTPA were estimated to be 1.9 and 0.01 mg/30μmol Zn-DTPA, respectively. The concentration of metals in the liver, kidneys, brain and femurs remained unchanged. These results suggest that almost all of Zn-DTPA is excreted into the urine without replacement with other metals, and so this chelating agent may not induce any deficiencies of essential metals when animals are treated with a dose of 30 µmol/kg per day.

Selenium (Se) concentrations in plasma, urine, and feces were determined by PIXE analysis before and after intravenous (iv) / oral (po) administration of sodium selenite (a dose equivalent to 2 mg/kg of selenium) to rats. The concentration-time profiles of Se were analyzed by a pharmacokinetic approach. The plasma Se profile after iv injection was biphasic and well-fit to a 2-compartment open model, showing two half lives (t1/2). The first t1/2 was about 0.3 hr and the second t1/2 was 6.9 hrs. The plasma concentration reached almost basal level after about 80 hrs of injection. On the other hand, plasma profiles after po administration showed absorption rate-limiting elimination. The bioavailability of oral sodium selenite (about 49%) and significantly higher amount of fecal Se excretion indicated relatively poor intestinal absorption of sodium selenite, compared to the previously published data. Urinary Se excretion was almost comparable between iv and po groups. The total recovery of the dose excreted in urine and feces was 30 ± 10 % in iv and 56 ± 15 % in po group. The renal excretion was considered to be a major route of Se excretion after absorption. Significant amount of Se that was not fully excreted was noted, suggesting Se distribution or accumulation in organs, together with volatile excretion.