[Effects of EDTPO on hard tissues in rats. 2. Changes of serum components and morphology of hard tissues due to various doses of EDTPO].

Dose dependent effects of EDTPO on morphology and mineralization of hard tissues as well as calcium (Ca), inorganic phosphorus (IP) and alkaline phosphatase (ALP) levels in serum were examined in growing rats. Five groups of male S.D. rats weighing 110-120g were received s.c. injections of 0 (control), 1, 2, 4, and 8mg P/kg body wt. of EDTPO once daily (at noon) for 10 days respectively. Tetracycline (Tc.) were i.p. injected three times, one day before drug treatment (1st), 5th (2nd) and 10th (3rd) day of experimental period. All rats were received i.p. injection of 185kBq (5 microCi) of 45Ca six hours after the 10th injection of EDTPO. On the next day, blood samples were taken from the carotid artery. Then the animals were killed and both tibias, submandibular teeth and right femur were removed. Serum Ca, IP and ALP were determined by spectrophotometry. Wet, dry and ash bone weight were measured and bone calcium was determined by atomic absorption method. 45Ca activity was counted by the liquid scintillation counter. Serum Ca levels revealed decreasing tendency at the dose of 1mg P/kg and 2mg P/kg of EDTPO but increasing tendency at 4mg P/kg and significant increase at the dose of 8mg P/kg. Specific activity of 45Ca in serum increased slightly at 2mg P/kg, but at the dose of 8mg P/kg increased five times compared to that of control. Decrease of IP and increase of ALP level were observed only at the dose level of 8mg P/kg. Wet, dry, and ash weight, and Ca content of femur and 45Ca activity were decreased dose-dependently. In histological examination, changes of tibia and teeth were observed at the dose of 2mg P/kg and following dose increase these changes were more significantly. Ultraviolet line of Tc. appeared three in proximal metaphysis of tibia and dentin at the dose of 1mg P/kg and 2mg P/kg, but at the dose of 4mg P/kg and 8mg P/kg 2nd and 3rd line could not be detected. These result indicated that the effects of EDTPO on serum ingredients, long bone and teeth are initiated at the dose of 2mg P/kg, appeared at the dose of 4mg P/kg significantly, and at the dose of 8 mg P/kg severely. In addition, increase of the ratio of 45Ca specific activity between serum and bone observed at the dose of 4mg P/kg and 8mg P/kg suggested that these effects of EDTPO would be due to inhibitory action on mineralization.