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.

Ca-DTPA and Zn-DTPA were injected intraperitoneally into rats with a dose of 30 or 300 µmol/kg. The blood was collected from the tail vein just before the injection, 3, 6 and 24 hours after the injection. and centrifuged 10 separate the plasma. These plasma samples were analyzed by PIXE at Nishina Memorial Cyclotron Center.

Sodium, potassium, calcium, iron, copper and zinc were detected in the plasma. Ca-DTPA significantly lowered the concentration of zinc, while no significant changes were observed in the other metals. Zn-DTPA did not lower any metal concentrations, but a significant increase of plasma zinc was observed.

In conclusion, Ca-DTPA was confirmed to induce hypozincemia, which may be the cause of fetal injuries such as abortion, fetal death and malformation. Zn-DTPA was suggested not to induce any deficiencies of essential metals.

Ca-DTPA or Zn-DTPA was injected subcutaneously to pregnant mice once a day for 5 consecutive days from the 13th day to the 17th day of gestation. Maternal and fetal livers were collected 20 hours after the final injection of DTPA, and essential metal contents in the liver samples were determined by PIXE.

Both Ca-DTPA and Zn-DTPA don't affect any essential metals in the maternal liver, but Ca-DTPA decreases copper and zinc contents in the fetal liver to 2/3 and 1/2 of the control values, respectively. Although Zn-DTPA does not affect fetal zinc content, it decreases that of copper. It could not be determined whether DTPA affects fetal manganese content or not because the fetal liver contains no detectable amount of manganese.