A new approach to studying inhibitors of calcium oxalate crystal growth.
The nucleation and crystal growth of calcium oxalate (CaOx) were studied at pH 5.5 using turbidimetric measurements at 620 nm of suspensions produced by mixing calcium chloride and sodium oxalate (initial conditions: Ca, 3 x 10(-3) M; Ox, 0.5 x 10(-3) M). CaOx crystallization kinetics were defined first by the induction time ti and then by the slope of turbidity as a function of time during the interval corresponding to a correlation coefficient r2 > 0.99. The technique described requires only a small amount of material, is quick, convenient, and can be used to study inhibitors of CaOx crystallization by comparing ti and the rate of crystal growth in the presence and absence of inhibitors. The effects on CaOx crystal growth of several low molecular weight compounds, i.e. di- and tricarboxylic acids, were examined. The majority of these compounds were inhibitors of crystal growth, the greatest effect being seen with citric acid (50% inhibition in the presence of 1.5 x 10(-3) M citric acid), isocitric acid (50% inhibition in the presence of 0.75 x 10(-3) M isocitric acid) and pyrophosphate (30% inhibition in presence of 0.15 x 10(-3) M pyrophosphate). The inhibitors' behaviour regarding the medium was studied without any assumptions about their possible mechanisms of action. Measurements of ionized calcium before and after the reaction, as well as the observation of crystals by scanning electron microscopy, allowed us to formulate the hypothesis that the effect of citric acid and tartaric acid can be attributed mainly to ion pairing, in contrast to that of pyrophosphate and the other carboxylic acids.
Laboratoire de Biochimie A, Hôpital Necker-Enfants malades, Paris, France.
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Hennequin
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Lalanne
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Daudon
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Lacour
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Drueke
D002118:Calcium / Q000737:chemistry; D002129:Calcium Oxalate / Q000737:chemistry*; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D003460:Crystallization; D011756:Diphosphates / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007477:Ions; D007523:Isocitrates / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D014545:Urinary Calculi / Q000737:chemistry* / Q000517:prevention & control* / Q000648:ultrastructure
D002951:Citrates; D011756:Diphosphates; D007477:Ions; D007523:Isocitrates; D002129:Calcium Oxalate; D019343:Citric Acid; C034219:isocitric acid; D002118:Calcium