Enhanced sensitivity of young suckling rats to the toxic effects of 1,25-dihydroxyvitamin D3.

Abstract

The responses of suckling rat pups of different ages to high doses of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) were determined. Four daily oral doses of 1,25(OH)2D3 (2 ng/g body wt) given to 9–13-day-old pups produced severe hypercalcemia 24 h after the last dose (15.52 ± 0.14 mg/dl vs. 10.94 ± 0.15 mg/dl in controls of the same age) and a 9-fold increase in kidney Ca content; the same doses given to 16–20-day-old pups produced only modest hypercalcemia (12.34 ± 0.22 mg/dl vs. 10.57 ± 0.22 mg/dl in controls of the same age) and a 4-fold increase in kidney Ca content. There was no change in serum phosphorus (P) at either age. Six-week-old weaned rats, given the same doses of 1,25(OH)2D3, showed neither hypercalcemia nor kidney calcification and thus were protected against the toxic effects of the treatment. The difference in responses of the twoages of suckling pups was also observed with lower doses. Removal of the solid food from the diet of the 16–20-day pups showed that the consumption of solid food, in addition to milk, in this age group was not the cause of the lower serum Ca response. The changes in both serum and kidney Ca after intraperitoneal (i.p.) injections of 1,25(OH)2D3 at the same dose in each age group were similar to those observed with oral administration. The time course of the rise in serum Ca following a single dose of 1,25(OH)2D3, given either orally or i.p., showed that the hypercalcemia was more pronounced and lasted longer in the 9–13-day pups than in the 16–20-day pups. The results suggest that weaned rats are relatively well protected against hypervitaminosis D and that younger pups gradually develop such protection during the suckling period.