Comparative effects of calcitriol and parathyroid hormone on serum aluminum in vitamin D-depleted rabbits fed an aluminum-supplemented diet.

J F Long, L A Nagode, C L Steinmeyer, G Renkes
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Abstract

Under normal circumstances, the body barriers effectively limit the entry and retention of dietary aluminum. However, both parathyroid hormone (PTH) and calcitriol (physiologically active hormonal form of vitamin D3) have been reported to produce elevation of serum aluminum in animals fed an aluminum-supplemented ration. To compare the effects of calcitriol with those of PTH with reference to their putative effect to enhance aluminum absorption, an experiment was designed wherein the serum levels of both PTH and calcitriol would be changing markedly during a short time-frame. To condition the rabbits used for this comparison, they were fed a vitamin D-free diet, which caused the level of calcitriol and its precursors to decline rapidly. The calcitriol deficit together with the ensuing lack of calcium absorption resulted in a state of secondary hyperparathyroidism. Vitamin D-depletion was shown to be complete by the high level of serum PTH and a low (unmeasurable) level of serum calcitriol. To enable comparison of PTH with calcitriol, exogenous calcitriol infusion (60 IU/day) was started by osmotic pump simultaneously with the beginning of an aluminum (aluminum lactate) supplemented diet. Aliquots were collected for both serum PTH and serum calcitriol at intervals during the 7 day study. A rising serum aluminum level was highly correlated with the rising serum calcitriol level in the rabbits (r = 0.903, p = 0.036) during the first 4 days of the infusion. The mean serum aluminum levels rose nearly 13 parts per billion (ppb) in the 7 day period. Declining serum PTH (due to feedback mechanisms of calcitriol suppressing PTH synthesis) showed a negative correlation of serum aluminum and serum PTH (r = -0.959, p = < 0.01) during the first 4 days of infusion. Control rabbits (vitamin-D depleted) fed aluminum-supplemented rations have shown only a minimal transient rise in serum aluminum level which returned to the pre-test level by the end of the week. To test for any effect of PTH on serum aluminum in the absence of calcitriol, five rabbits were implanted with osmotic pumps infusing PTH (mean 6.0 U/hr) and started on an aluminum supplemented diet. These rabbits, having previously been depleted of vitamin D were already in a state of nutritional secondary hyperparathyroidism as shown by their elevated pretest PTH levels. During the 7 day infusion, the serum aluminum rose only a mean of approximately 1 part per billion (ppb).(ABSTRACT TRUNCATED AT 400 WORDS)

骨化三醇和甲状旁腺激素对补铝饲粮中维生素d缺失家兔血清铝的影响。
在正常情况下,人体屏障有效地限制了膳食铝的进入和滞留。然而,据报道,甲状旁腺激素(PTH)和骨化三醇(维生素D3的生理活性激素形式)在饲喂补铝日粮的动物中引起血清铝的升高。为了比较骨化三醇和甲状旁腺激素对铝吸收的影响,我们设计了一项实验,其中甲状旁腺激素和骨化三醇的血清水平在短时间内会发生显著变化。为了使兔子适应这种比较,他们被喂食不含维生素d的食物,这导致骨化三醇及其前体的水平迅速下降。骨化三醇缺乏症和随后的钙吸收不足导致继发性甲状旁腺功能亢进。高水平的血清甲状腺激素和低水平(无法测量)的血清骨化三醇显示了维生素d的消耗。为了比较PTH与骨化三醇的差异,在开始添加铝(乳酸铝)的同时,通过渗透泵开始外源性骨化三醇输注(60 IU/天)。在7天的研究中,每隔一段时间收集一次血清甲状旁腺激素和骨化三醇的等量。在给药前4天,家兔血清铝水平升高与骨化三醇水平升高高度相关(r = 0.903, p = 0.036)。在7天期间,平均血清铝水平上升了近十亿分之十三(ppb)。注射前4天血清PTH下降(由于骨化三醇抑制PTH合成的反馈机制),血清铝与血清PTH呈负相关(r = -0.959, p = < 0.01)。对照组(缺乏维生素d)饲喂补铝口粮,血清铝水平只有短暂的微小上升,到一周结束时又恢复到试验前的水平。为了检测在骨化三醇不存在的情况下甲状旁腺激素对血清铝的影响,5只家兔被植入注入甲状旁腺激素的渗透泵(平均6.0 U/hr),并开始补铝饮食。这些兔子,先前已经耗尽了维生素D,已经处于营养性继发性甲状旁腺功能亢进的状态,从它们的PTH水平升高可以看出。在7天的输注期间,血清铝仅平均上升约1十亿分之一(ppb)。(摘要删节为400字)
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