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PLoS One. 2018 Aug 29;13(8):e0198881. doi: 10.1371/journal.pone.0198881. eCollection 2018.

Xanthine urolithiasis: Inhibitors of xanthine crystallization.

Author information

1
Laboratory of Renal Lithiasis Research, Faculty of Sciences, University Institute of Health Sciences Research (IUNICS-IdISBa), University of Balearic Islands, Palma de Mallorca, Spain.

Abstract

OBJECTIVE:

To identify in vitro inhibitors of xanthine crystallization that have potential for inhibiting the formation of xanthine crystals in urine and preventing the development of the renal calculi in patients with xanthinuria.

METHODS:

The formation of xanthine crystals in synthetic urine and the effects of 10 potential crystallization inhibitors were assessed using a kinetic turbidimetric system with a photometer. The maximum concentration tested for each compound was: 20 mg/L for 3-methylxanthine (3-MX); 40 mg/L for 7-methylxanthine (7-MX), 1-methylxanthine (1-MX), theobromine (TB), theophylline, paraxanthine, and caffeine; 45 mg/L for 1-methyluric acid; 80 mg/L for 1,3-dimethyluric acid; and 200 mg/L for hypoxanthine. Scanning electron microscopy was used to examine the morphology of the crystals formed when inhibitory effects were observed.

RESULTS:

Only 7-MX, 3-MX, and 1-MX significantly inhibited xanthine crystallization at the tested concentrations. Mixtures of inhibitors had an additive effect rather than a synergistic effect on crystallization.

CONCLUSION:

Two of the inhibitors identified here-7-MX and 3-MX-are major metabolites of TB. In particular, after TB consumption, 20% is excreted in the urine as TB, 21.5% as 3-MX, and 36% as 7-MX. Thus, consumption of theobromine could protect patients with xanthinuria from the development of renal xanthine calculi. Clinical trials are necessary to demonstrate these effects in vivo.

PMID:
30157195
PMCID:
PMC6114289
DOI:
10.1371/journal.pone.0198881
[Indexed for MEDLINE]
Free PMC Article

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