Effect of crystallization inhibitors on vascular calcifications induced by vitamin D: a pilot study in Sprague-Dawley rats

Abstract

Background: Pathological calcification in soft tissues (ie, ectopic calcification) can have severe consequences. Hydroxyapatite is the common mineral phase present in all tissue calcifications. In general, the development of tissue calcifications requires a pre-existing injury as an inducer (heterogeneous nucleant), whereas further progression requires the presence of other promoter factors (such as hypercalcemia and/or hyperphosphatemia) and/or a deficiency in calcification repressor factors (crystallization inhibitors and cellular defense mechanisms). The present study investigated the capacity of etidronate (a bisphosphonate used in osteoporosis treatment) and phytate (a natural product) to inhibit vascular calcification in rats.

Methods and results: Six male Sprague-Dawley rats in each of the 3 treatment groups were subcutaneously injected with either a placebo (physiological serum solution), etidronate (0.825 micromol x kg(-1) x day (-1)) or phytate (0.825 micromol x kg (-1) x day(-1)) for 8 days. Four days into this regimen, calcinosis was induced by subcutaneous injections of 500,000 IU/kg vitamin D at 0 h, 24 h and 48 h. Ninety-six hours after the final vitamin D injection, the rats were killed and aortas and their hearts were removed for histological and calcium analyses. The data showed that phytate-treated rats had lower levels of aortic calcium than placebo-treated rats. All groups had similar heart calcium levels.

Conclusions: The present study found that phytate acted as a vascular calcification inhibitor. Thus, the action of polyphosphates could be important in protecting against vascular calcification.