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1,25-Dihydroxyvitamin D3 increases serum and tissue accumulation of aluminum in rats
Abstract:
We examined the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in both hypercalcemic and hypocalcemic rat models and the effect of exogenous 25-hydroxyvitamin D3 (25(OH)D3) on serum and tissue aluminum (Al) burdens. Rats fed a 0.2% Al diet received daily subcutaneous injections of either 1,25(OH)2D3 (80.9 ng/kg, n = 5 and 809 ng/kg, n = 8), 25 (OH)D3 (809 ng/kg, n = 4, and 8090 ng/kg, n = 8) or propylene glycol vehicle for 18 days. Rats given 809 ng/kg of 1,25(OH)2D3 were hypercalcemic and when compared with pair-fed controls had higher serum (33.1 vs. 14.3 micrograms/L, P less than 0.01), bone (21.2 vs. 13.2 micrograms/gm, P less than 0.01), and kidney (6.5 vs. 2.0 micrograms/gm, P less than 0.01) but not brain (1.2 vs. 1.5 micrograms/gm) or liver (0.9 vs. 0.8 micrograms/gm dry tissue) Al concentration. The lower dose of 1,25(OH)2D3 had no effect on serum or tissue Al. Treatment with 25(OH)D3 did not increase serum Ca and Al or tissue Al concentration. To dissociate a specific effect of exogenous 1,25(OH)2D3 from the concurrent hypercalcemia, endogenous production of 1,25(OH)2D3 was stimulated. Animals were fed a low Ca diet until hypocalcemia developed and were then divided into four groups: one given low Ca (n = 7) for 21 days, one given low Ca plus 0.2% Al (n = 7) for 21 days, one returned to a normal Ca diet (n = 4) for 30 days, and one returned to a normal Ca diet for 9 days and continued with a normal diet plus 0.2% Al (n = 5) for 21 days. Hypocalcemic rats fed the Al diet, when compared with hypocalcemic controls, had higher serum (143.6 vs. 31.8 micrograms/L, P less than 0.01), bone (16.0 vs. 2.9 micrograms/gm, P less than 0.01), and kidney (8.2 vs. 2.8 micrograms/gm, P less than 0.005) but not brain (3.4 vs. 2.3 micrograms/gm) or liver (3.8 vs. 2.3 micrograms/gm) Al concentrations. Serum, bone, and kidney Al concentration was also significantly higher than that in normocalcemic rats fed the Al diet. These results indicate that pharmacologic doses of 1,25(OH)2D3 and dietary hypocalcemia enhance gastrointestinal Al absorption and serum, kidney, and bone Al concentration.