Phytate (Myo-inositol hexakisphosphate) inhibits cardiovascular calcifications in rats

Abstract

Calcification is an undesirable disorder, which frequently occurs in the heart vessels. In general, the formation of calcific vascular lesions involves complex physicochemical and molecular events. Calcification (hydroxyapatite) is initiated by injury and is progressed by promoter factors and/or the deficit of inhibitory signals. Myo-inositol hexakisphosphate (phytate, InsP6) is found in organs, tissues and fluids of all mammals and exhibits an important capacity as a crystallization inhibitor of calcium salts in urine and soft tissues. The levels found clearly depend on the dietary intake but it can also be absorbed topically. In this paper, the capacity of InsP6 as a potential inhibitor of cardiovascular calcifications was assessed in Wistar rats. Three groups were included, a control group, an InsP6 treated group (subjected to calcinosis induction by Vitamin D and nicotine and treated with standard cream with a 2% of InsP6 as potassium salt) and an InsP6 non-treated group (only subjected to calcinosis induction). All rats were fed AIN 76-A diet (a purified diet in which InsP6 is undetectable). Animals were monitorized every 12 hours. After 60 hours of calcinosis treatment, all rats of the InsP6 non-treated group died and the rest were sacrificed. Aortas and hearts were removed. A highly significant increase in the calcium content of aorta and heart tissue was observed in the InsP6 non-treated rats (21 +/- 1 mg calcium/g dry aorta tissue, 10 +/- 1 mg calcium/g dry heart tissue) when compared with controls (1.3 +/- 0.1 mg calcium/g dry aorta tissue, 0.023 +/- 0.004 mg calcium/g heart dry tissue) and InsP6 treated (0.9 +/- 0.2 mg calcium/g dry aorta tissue, 0.30 +/- 0.03 mg calcium/g dry heart tissue) animals. Only InsP6 non-treated rats displayed important mineral deposits in aorta and heart. These findings are consistent with the action of InsP6, as an inhibitor of calcification of cardiovascular system.

Effect of Crystallization Inhibitors on Vascular Calcifications Induced by Vitamin D A Pilot Study in Sprague-Dawley Rats

“…A previous study using both vitamin D (300,000 IU/kg im) and nicotine (25 mg/kg po) reported higher levels of calcification in the rats' arteries and hearts compared with the current study. 32 That study used lower levels of vitamin D, and thus involved lower levels of calcium phosphate supersaturation than the present study. These observations demonstrate the importance of a preexisting lesion (caused by nicotine in the other study) in the development of tissue calcification.…”

“…A previous study found that phytate could inhibit vitamin D and nicotine-induced calcification in both the aorta and the heart of Wistar rats. 32 The difference between the findings of the 2 studies may be related to less lesions in the absence of nicotine, and that as a consequence of the higher hydroxyapatite supersaturation (because of increased blood calcium and phosphorus levels), the calcium deposits may have developed directly through homogeneous nucleation and not as a consequence of hydroxyapatite heterogeneous nucleation induced by the injured tissue. The tissue calcium content data for the 2 studies shows that more calcium was deposited when using vitamin D and nicotine than using only high vitamin D doses, despite the former experiments being half the duration of the latter.…”

“…In general, crystallization inhibitors bind to the crystal nucleus or to the crystal face and hence prevent or disturb crystal development without any cellular signaling capacity. Pyrophosphate, 28 bisphosphonates (such as etidronate, alendronate and ibandronate) [29][30][31] and phytate (myoinositol hexakisphosphate) 32 have been shown to inhibit crystallization in the form of vascular calcification. Etidronate is used to treat osteoporosis, 33 and phytate is a naturally occurring compound that can either be ingested 34,35 or absorbed topically.…”

Detection, removal and prevention of calculus: Literature Review

“…They also affect the quality and quantity of calcium phosphate crystals. Zinc salts have been reported to reduce plaque acidogenicity and growth (Grases et al, 2006). Toothpastes containing zinc salts, such as zinc citrate and zinc chloride, have been shown to be effective in deceasing calculus formation.…”

Pericardial Processing: Challenges, Outcomes and Future Prospects

“…Proanthocyanidin-treated pericardial tissues are non-cytotoxic and resist against enzyme digestion, and have been shown to be compatible with cell attachment and proliferation. Phytate has been suggested as an anticalcification reagent (Grases et al, 2006(Grases et al, , 2008 and has achieved promising results, to be validated by further studies. Other amide-type crosslinks, based on the activation of carboxyl groups, have been studied, such as diphenylphosphorylazide or ethyldimethylaminopropyl carbodiimide.…”