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  • Theobromine inhibits uric acid crystallization. A potential application in the treatment of uric acid nephrolithiasis.

Theobromine inhibits uric acid crystallization. A potential application in the treatment of uric acid nephrolithiasis.

PloS one (2014-10-22)
Felix Grases, Adrian Rodriguez, Antonia Costa-Bauza
ABSTRACT

To assess the capacity of methylxanthines (caffeine, theophylline, theobromine and paraxanthine) to inhibit uric acid crystallization, and to evaluate their potential application in the treatment of uric acid nephrolithiasis. The ability of methylxathines to inhibit uric acid nucleation was assayed turbidimetrically. Crystal morphology and its modification due to the effect of theobromine were evaluated by scanning electron microscopy (SEM). The ability of theobromine to inhibit uric acid crystal growth on calculi fragments resulting from extracorporeal shock wave lithotripsy (ESWL) was evaluated using a flow system. The turbidimetric assay showed that among the studied methylxanthines, theobromine could markedly inhibit uric acid nucleation. SEM images showed that the presence of theobromine resulted in thinner uric acid crystals. Furthermore, in a flow system theobromine blocked the regrowth of post-ESWL uric acid calculi fragments. Theobromine, a natural dimethylxanthine present in high amounts in cocoa, acts as an inhibitor of nucleation and crystal growth of uric acid. Therefore, theobromine may be clinically useful in the treatment of uric acid nephrolithiasis.

MATERIALS
Product Number
Brand
Product Description

Supelco
Theophylline, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Melting point standard 235-237°C, analytical standard
Caffeine for system suitability, European Pharmacopoeia (EP) Reference Standard
USP
Theophylline, United States Pharmacopeia (USP) Reference Standard
Theophylline, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Theophylline, anhydrous, ≥99%, powder
Sigma-Aldrich
Theobromine, ≥98.0%
Supelco
Theobromine, analytical standard
Supelco
Caffeine Melting Point Standard, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Caffeine, Pharmaceutical Secondary Standard; Certified Reference Material
Caffeine, European Pharmacopoeia (EP) Reference Standard
Supelco
Caffeine, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Sigma-Aldrich
Caffeine, anhydrous, 99%, FCC, FG
Sigma-Aldrich
Caffeine, anhydrous, tested according to Ph. Eur.
Supelco
Mettler-Toledo Calibration substance ME 18872, Caffeine, traceable to primary standards (LGC)
Sigma-Aldrich
1,7-Dimethylxanthine, ~98%, solid
Sigma-Aldrich
Caffeine, powder, ReagentPlus®
Sigma-Aldrich
Caffeine, Sigma Reference Standard, vial of 250 mg
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Caffeine, meets USP testing specifications, anhydrous
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Uric acid, BioXtra, ≥99% (HPLC)
Sigma-Aldrich
Caffeine, BioXtra
Sigma-Aldrich
Uric acid, ≥99%, crystalline
USP
Caffeine, United States Pharmacopeia (USP) Reference Standard
USP
Caffeine melting point standard, United States Pharmacopeia (USP) Reference Standard