A New Perspective of Gallic Acid on Calcium Oxalate Nucleation

Abstract

The therapeutics for nephrolithiasis have created an awareness of the potential effects of crystal modifiers on the biocrystallization process. The crystallization of calcium oxalate, a primary constituent of kidney stones, is confirmed to be inhibited by natural or synthetic modifiers, but the induction of calcium oxalate dihydrate and trihydrate, which is likewise effective for retardation of stone formation, is rarely focused on. Herein, we performed a systematic investigation of the effect of gallic acid, a natural polyphenol, on the nucleation of calcium oxalate from both experimental and simulation approaches. Our results reveal that the solution species of gallic acid alter the nucleation pathways of calcium oxalate and induce the formation of different types of amorphous structures corresponding to calcium oxalate hydrates. Different species of gallic acid regulate the formation of three types of amorphous calcium oxalates (ACOs) by incorporating the proper water contents and specific interactions. Fluorescence microscopy further demonstrates clearly the incorporation of gallic acid in the nucleated calcium oxalate precipitates. These findings unveil the nucleation mechanism of different calcium oxalate hydrates with the inclusion of modifiers and provide insights for an understanding of stone formation and its potential inhibitors.

Calcium Oxalate and Gallic Acid: Structural Characterization and Process Optimization toward Obtaining High Contents of Calcium Oxalate Monohydrate and Dihydrate

“…The oxidation peak of GA was confirmed with the addition of GA in both samples (c = 0.02 mM) where a more pronounced broad shoulder was observed at the same potential (E = 0.34 V) in both samples, which confirms that GA was captured in calcium oxalate clusters. The obtained data agree with the literature, since, in pure hydrate form (run 15), the adsorption of GA did not occur, while in the other two runs (runs 15 and 17), where the presence of GA resulted in a mixture of three hydrate forms, gallic acid was captured in the calcium oxalate clusters [22]. It was also observed that, if the proportion of individual hydrates is less than 10%, GA will not be visible in the cyclic voltammogram (Figure S2).…”

“…ions possibly interact with C 2 O 4 2− and GA − leading to the formation of calcium oxalate clusters by specific interactions [22]. This could potentially indicate that gallic acid could be an efficient inhibitor or modulator towards obtaining specific hydrate modifications of calcium oxalate.…”

“…The effect of gallic acid on the formation of kidney stones, and especially calcium oxalate, has not been fully investigated. Li et al [22] revealed in their work that gallic acid can alter the nucleation pathways of calcium oxalate, which eventually leads to the formation of three different hydrate structures. The investigation of the influence of individual physiological parameters on calcium oxalate formation is especially welcomed as it could contribute to the elucidation of crystal growth and nucleation mechanisms in urolithiasis.…”

Natural inhibitors from earthworms for the crystallization of calcium oxalate monohydrate

“…The formation of COD may be due to the inhibitor affecting the nucleation and growth process of CaOx and the presence of proteins stabilizes the existence of the COD form. Li et al 43,44 believed that the presence of additives such as citric acid can alter this crystallization pathway by modulating the water activity and the intermolecular interactions.…”

Effect of L-alanyl-glycine dipeptide on calcium oxalate crystallization in artificial urine

“…Crystal growth modifiers are small amounts of additives that can be used to either promote or inhibit crystallization/transformation processes. Several types of additives, such as amino acids [21][22][23][24][25][26][27][28], proteins [29,30], carboxylic acids [31][32][33] and polymers [34][35][36] have been shown to affect CaOx crystallization. In addition, studies have shown that peptides containing aspartic acidglutamic acid, glutamic acid-glutamic acid, alanine-aspartic acid amino acids have a profound effect on the CaOx crystals and could promote the formation of COD and COT crystals and stabilize these metastable phases over very long periods of time [37][38][39][40][41][42].…”